B cell

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This article is about cell biology. For the electrical term, see: B battery.

The cells of the immune system that make antibodies to invading pathogens like viruses.
They form memory cells that remember the same pathogen for faster antibody production in
future infections.
B cells are lymphocytes that play a large role in the humoral immune response (as opposed to
the cell-mediated immune response, which is governed by T cells). The principal functions of
B cells are to make antibodies against antigens, perform the role of antigen-presenting cells
(APCs) and eventually develop into memory B cells after activation by antigen interaction. B
cells are an essential component of the adaptive immune system.
The abbreviation "B", in B cell, comes from the bursa of Fabricius in birds, where they
mature. In mammals, immature B cells are formed in the bone marrow, which is used as a
backronym for the cells' name.[1]

Contents
[hide]
• 1 Development of B cells
• 2 Immune Tolerance
• 3 Functions
○ 3.1 Clonality
○ 3.2 B cell types
• 4 Recognition of antigen by B cells
• 5 Activation of B cells
○ 5.1 T cell-dependent activation
○ 5.2 T cell-independent activation
• 6 The ancestral roots of B cells
 • 7 Origin of the term
• 8 B cell-related pathology
• 9 Additional image
• 10 See also
• 11 References
• 12 External links

[edit] Development of B cells

Immature B cells are produced in the bone marrow of most mammals. Rabbits are an
exception; their B cells develop in the appendix-sacculus rotundus. After reaching the IgM+
immature stage in the bone marrow, these immature B cells migrate to the spleen, where they
are called transitional B cells, and some of these cells differentiate into mature B
lymphocytes.[2]
B cell development occurs through several stages, each stage representing a change in the
genome content at the antibody loci. An antibody is composed of two identical light (L) and
two identical heavy (H) chains, and the genes specifying them are found in the 'V' (Variable)
region and the 'C' (Constant) region. In the heavy-chain 'V' region there are three segments;
V, D and J, which recombine randomly, in a process called VDJ recombination, to produce a
unique variable domain in the immunoglobulin of each individual B cell. Similar
rearrangements occur for light-chain 'V' region except there are only two segments involved;
V and J. The list below describes the process of immunoglobulin formation at the different
stages of B cell development.
IL-7
Stage Heavy chain Light chain Ig CD19?
receptor?
Progenitor (or
germline germline - Yes No
pre-pro) B cells
Early Pro (or undergoes D-J
germline - Yes No
pre-pre)-B cells rearrangement
Late Pro (or pre- undergoes V-DJ
germline - Yes Yes[3]
pre)-B cells rearrangement
IgM in
Large Pre-B cells is VDJ rearranged germline Yes[4] Yes
cytoplasm
undergoes V-J IgM in
Small Pre-B cells is VDJ rearranged Yes Yes
rearrangement cytoplasm
IgM on
Immature B cells is VDJ rearranged VJ rearranged No Yes
surface
IgM and IgD
Mature B cells is VDJ rearranged VJ rearranged No Yes
on surface
When the B cell fails in any step of the maturation process, it will die by a mechanism called
apoptosis, here called clonal deletion.[5] B cells are continuously produced in the bone
marrow. When B cell receptors on the surface of the cell matches the detected antigens
present in the body, the B cell proliferates and secretes a free form of those receptors
(antibodies) with identical binding sites as the ones on the original cell surface. After
activation, the cell proliferates and B memory cells would form to recognise the same
antigen. This information would then be used as a part of the adaptive immune system for a
more efficient and more powerful immune response for future encounters with that antigen.
B cell membrane receptors evolve and change throughout the B cell life span.[6] TACI,
BCMA and BAFF-R are present on both immature B cells and mature B cells. All of these 3
receptors may be inhibited by Belimumab. CD20 is expressed on all stages of B cell
development except the first and last; it is present from pre-B cells through memory cells, but
not on either pre-pro-B cells or plasma cells.[7]
[edit] Immune Tolerance
Like their fellow lymphocytes, the T cells, immature B cells are tested for auto-reactivity by
the immune system before leaving the bone marrow. In the bone marrow (the central
lymphoid organ), central tolerance is produced. The immature B cells whose B cell Receptors
(BCRs) bind too strongly to self antigens will not be allowed to mature. If B cells are found
to be highly reactive to self, three mechanisms can occur.
• Clonal deletion: the removal, usually by apoptosis, of B cells of a particular self
antigen specificity.
• Receptor editing: the BCRs of self reactive B cells are given an opportunity to
rearrange their conformation. This process occurs via the continued expression of the
Recombination activating gene (RAG). Through the help of RAG, receptor editing
involves light chain gene rearrangement of the B cell receptor. If receptor editing fails
to produce a BCR that is less autoreactive, apoptosis will occur. Note that defects in
the RAG-1 and RAG-2 genes are implicated in Severe Combined Immunodeficiency
(SCID). The inability to recombine and generate new receptors lead to failure of
maturity for both B cells and T cells.
• Anergy: B cells enter a state of permanent unresponsiveness when they bind with
weakly cross-linking self antigens that are small and soluble.
[edit] Functions
The human body makes millions of different types of B cells each day that circulate in the
blood and lymphatic system performing the role of immune surveillance. They do not
produce antibodies until they become fully activated. Each B cell has a unique receptor
protein (referred to as the B cell receptor (BCR)) on its surface that will bind to one particular
antigen. The BCR is a membrane-bound immunoglobulin, and it is this molecule that allows
the distinction of B cells from other types of lymphocyte, as well as being the main protein
involved in B cell activation. Once a B cell encounters its cognate antigen and receives an
additional signal from a T helper cell, it can further differentiate into one of the two types of
B cells listed below (plasma B cells and memory B cells). The B cell may either become one
of these cell types directly or it may undergo an intermediate differentiation step, the
germinal center reaction, where the B cell will hypermutate the variable region of its
immunoglobulin gene ("somatic hypermutation") and possibly undergo class switching.
Other functions for B cells include antigen presentation, cytokine production and lymphoid
tissue organization.
[edit] Clonality
B cells exist as clones. All B cells derive from a particular cell, and thus, the antibodies their
differentiated progenies (see below) produce can recognize and/or bind the same specific
surface components composed of biological macromolecules (epitope) of a given antigen.
Such clonality has important consequences, as immunogenic memory relies on it. The great
diversity in immune response comes about because there are up to 109 clones with
specificities for recognizing different antigens. A single B cell or a clone of cells with shared
specificity, upon encountering its specific antigen, divides to produce many B cells. Most of
such B cells differentiate into plasma cells that secrete antibodies into blood that bind the
same epitope that elicited proliferation in the first place. A small minority survives as
memory cells that can recognize only the same epitope. However, with each cycle, the
number of surviving memory cells increases. The increase is accompanied by affinity
maturation which induces the survival of B cells that bind to the particular antigen with high
affinity. This subsequent amplification with improved specificity of immune response is
known as secondary immune response. B cells that encounter antigen for the first time are
known as naive B cells.
[edit] B cell types

A suspected plasma cell. Plasma cells are normally detected in tissue rather than circulation.
• Plasma B cells (also known as plasma cells) are large B cells that have been exposed
to antigen and produce and secrete large amounts of antibodies, which assist in the
destruction of microbes by binding to them and making them easier targets for
phagocytes and activation of the complement system. They are sometimes referred to
as antibody factories. An electron micrograph of these cells reveals large amounts of
rough endoplasmic reticulum, responsible for synthesizing the antibody, in the cell's
cytoplasm. These are short lived cells and undergo apoptosis when the inciting agent
that induced immune response is eliminated. This occurs because of cessation of
continuous exposure to various colony stimulating factors required for survival.
• Memory B cells are formed from activated B cells that are specific to the antigen
encountered during the primary immune response. These cells are able to live for a
long time, and can respond quickly following a second exposure to the same antigen.
• B-1 cells express IgM in greater quantities than IgG and their receptors show
polyspecificity, meaning that they have low affinities for many different antigens.
Polyspecific immunoglobulins often have a preference for other immunoglobulins,
self antigens and common bacterial polysaccharides. B-1 cells are present in low
numbers in the lymph nodes and spleen and are instead found predominantly in the
peritoneal and pleural cavities.[8][9]
• B-2 cells are the conventional B cells most texts refer to.[citation needed]
• Marginal-zone B cells
• Follicular B Cells
[edit] Recognition of antigen by B cells
Mechanism of action.

T cell-dependent B cell activation, showing a TH2-cell (left), B cell (right), and several
interaction molecules
A critical difference between B cells and T cells is how each lymphocyte recognizes its
antigen. B cells recognize their cognate antigen in its native form. They recognize free
(soluble) antigen in the blood or lymph using their BCR or membrane bound-
immunoglobulin. In contrast, T cells recognize their cognate antigen in a processed form, as a
peptide fragment presented by an antigen presenting cell's MHC molecule to the T cell
receptor.
[edit] Activation of B cells
B cell recognition of antigen is not the only element necessary for B cell activation (a
combination of clonal proliferation and terminal differentiation into plasma cells). B cells that
have not been exposed to antigen, also known as naïve B cells, can be activated in a T cell-
dependent or -independent manner.
[edit] T cell-dependent activation
Once a pathogen is ingested by an antigen-presenting cell such as a macrophage or dendritic
cell, the pathogen's proteins are then digested to peptides and attached to a class II MHC
protein. This complex is then moved to the outside of the cell membrane. The macrophage is
now activated to deliver multiple signals to a specific T cell that recognizes the peptide
presented. The T cell is then stimulated to produce autocrines (Refer to Autocrine signalling),
resulting in the proliferation and differentiation to effector and memory T cells. Helper T
cells (i.e. CD4+ T cells) then activate specific B cells through a phenomenon known as an
Immunological synapse. Activated B cells subsequently produce antibodies which assist in
inhibiting pathogens until phagocytes (i.e. macrophages, neutrophils) or the complement
system for example clears the host of the pathogen(s).
Most antigens are T-dependent, meaning T cell help is required for maximal antibody
production. With a T-dependent antigen, the first signal comes from antigen cross linking the
B cell receptor (BCR) and the second signal comes from co-stimulation provided by a T cell.
T dependent antigens contain proteins that are presented on B cell Class II MHC to a special
subtype of T cell called a Th2 cell. When a B cell processes and presents the same antigen to
the primed Th cell, the T cell secretes cytokines that activate the B cell. These cytokines
trigger B cell proliferation and differentiation into plasma cells. Isotype switching to IgG,
IgA, and IgE and memory cell generation occur in response to T-dependent antigens. This
isotype switching is known as Class Switch Recombination (CSR). Once this switch has
occurred, that particular B cell will usually no longer make the earlier isotypes, IgM or IgD.
[edit] T cell-independent activation
Many antigens are T cell-independent in that they can deliver both of the signals to the B cell.
Mice without a thymus (nude or athymic mice that do not produce any T cells) can respond to
T independent antigens. Many bacteria have repeating carbohydrate epitopes that stimulate B
cells, by cross-linking the IgM antigen receptors in the B cell, responding with IgM synthesis
in the absence of T cell help. Conjugate vaccines are made to provide a stronger immune
response against these foreign molecules. There are two types of T cell independent
activation; Type 1 T cell-independent (polyclonal) activation, and type 2 T cell-independent
activation (in which macrophages present several of the same antigen in a way that causes
cross-linking of antibodies on the surface of B cells).
[edit] The ancestral roots of B cells
In an October 2006 issue of Nature Immunology, certain B cells of basal vertebrates (like fish
and amphibians) were shown to be capable of phagocytosis, a function usually associated
with cells of the innate immune system. The authors postulate that these phagocytic B cells
represent the ancestral history shared between macrophages and lymphocytes. B cells may
have evolved from macrophage-like cells during the formation of the adaptive immune
system.[10]
B cells in humans (and other vertebrates) are nevertheless able to endocytose antibody-fixed
pathogens, and it is through this route that MHC Class II presentation by B cells is possible,
allowing Th2 help and stimulation of B cell proliferation. This is purely for the benefit of
MHC Class II presentation, not as a significant method of reducing the pathogen load.
[edit] Origin of the term
The abbreviation "B" in B cell originally came from Bursa of Fabricius, an organ in birds in
which avian B cells mature.[11] When it was discovered that in most mammals immature B
cells are formed in bone marrow, the word B cell continued to be used, although other blood
cells also originate from pluripotent stem cells in the bone marrow. The fact that bone and
bursa both start with the letter 'B' is a coincidence.
[edit] B cell-related pathology
Aberrant antibody production by B cells is implicated in many autoimmune diseases, such as
rheumatoid arthritis and systemic lupus erythematosus. B cells are also susceptible of
malignant transformation.
[edit] Additional image

Figure 1: Schematic diagram to explain mechanisms of clonal selection of B cell, and how
secondary immune response is stronger, quicker and more specific in comparison with the
primary one.[12]
[edit] See also
• Affinity maturation
 • Antibody
• Clonal selection
• Original antigenic sin
[edit] References
1. ^ Alberts B, Johnson A, Lewis J, Raff M, Roberts k, Walter P (2002) Molecular Biology of
the Cell. Garland Science: New York, NY pg 1367.
2. ^ Allman D, Srivastava B, Lindsley RC (February 2004). "Alternative routes to maturity:
branch points and pathways for generating follicular and marginal zone B cells". Immunol.
Rev. 197: 147–60. doi:10.1111/j.0105-2896.2004.0108.x. PMID 14962193.
http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=0105-
2896&date=2004&volume=197&spage=147.
3. ^ "B Cell Development". Archived from the original on 2008-05-30.
http://web.archive.org/web/20080530012048/http://microvet.arizona.edu/Courses/MIC419/Tu
torials/Bcelldevelopment.html#generation. Retrieved 2008-09-20.
4. ^ "Immunology, Biology 328". http://bioweb.wku.edu/courses/biol328/Lecture11.html.
Retrieved 2008-09-20.
5. ^ Parham, P. (2005). The Immune System, Garland Science Publishing, New York, NY.
6. ^ "Hyperactive_Blymphocytes_lifespan_receptors".
http://www.healthvalue.net/Hyperactive_Blymphocytes_lifespan_receptors.html. Retrieved
2008-09-16.
7. ^ Bona, Constantin; Francisco A. Bonilla (1996). "5". Textbook of Immunology. Martin
Soohoo (2 ed.). CRC Press. pp. 102. ISBN 9783718605965.
8. ^ Montecino-Rodriguez, Encarnacion; Kenneth Dorshkind (2006-09). "New perspectives in
B-1 B cell development and function". Trends in Immunology (Elsevier B.V.) 27 (9): 428–
433. doi:10.1016/j.it.2006.07.005. PMID 16861037. http://www.sciencedirect.com/science?
_ob=ArticleURL&_udi=B6W7H-4KGG1T1-
2&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_v
ersion=1&_urlVersion=0&_userid=10&md5=923c447f162114b76b1a9ca6f3e02a06.
Retrieved 2008-05-05.
9. ^ Tung, James; Leonore A Herzenberg (2007-04). "Unraveling B-1 progenitors". Current
Opinion in Immunology (Elsevier B.V.) 19 (2): 150–155. doi:10.1016/j.coi.2007.02.012.
PMID 17303402. http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VS1-
4N2D5Y5-
6&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_vers
ion=1&_urlVersion=0&_userid=10&md5=f47493140685f1e9e8835d3cf7c1b2f5. Retrieved
2008-05.
10.^ J. Li, D.R. Barreda, Y.-A. Zhang, H. Boshra, A.E. Gelman, S. LaPatra, L. Tort & J.O.
Sunyer (2006). "B lymphocytes from early vertebrates have potent phagocytic and
microbicidal abilities". Nature Immunology 7 (10): 1116–1124. doi:10.1038/ni1389.
PMID 16980980.
11.^ Bursa of Fabricius
12.^ Goldsby, Richard; Kindt, TJ; Osborne, BA; Janis Kuby (2003). Immunology Fifth Edition.
New York: W. H. Freeman and Company. pp. 119–120. ISBN 0-07167-4947-5.

[edit] External links

• MeSH B-Lymphocytes
• B Cells and T Cells
• B Cell Development and Generation of Lymphocyte Diversity
 • Interactive Animation of B Cell Maturation (requires Flash video software)
• A Tale of Two SHEPherds (from Beaker Blog)
[show]v · d · eBlood: Lymphocytes

L B cellsPlasma · Memory · Follicular · Marginal-zone · Naive · Pre-B

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[show]v · d · eImmunology: Lymphocytic immune system

Antigen (Superantigen, Allergen) · Hapten

AntigensEpitope (Linear, Conformational) · Mimotope
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Macrophage · B cell
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toleranceinaction: Tolerance (Central, Peripheral, Clonal anergy, Clonal
deletion, Tolerance in pregnancy) · Immunodeficiency

ImmunogeneticSomatic hypermutation · V(D)J recombination · Junctional diversity ·

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Retrieved from "http://en.wikipedia.org/wiki/B_cell"
Categories: Lymphocytes | Human cells
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