B cell
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2008-07-15T05:01:22Z
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Reverted edits by [[Special:Contributions/124.217.84.190|124.217.84.190]] ([[User talk:124.217.84.190|talk]]) to last version by DOI bot
[[Image:Original antigenic sin.png|thumb|220px|right|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 [[lymphocyte]]s that play a large role in the [[humoral immunity|humoral immune response]] (as opposed to the [[cell-mediated immunity|cell-mediated immune response]], which is governed by [[T cell]]s). The principal function of B cells is to make [[antibody|antibodies]] against soluble [[antigen]]s. B cells are an essential component of the [[adaptive immune system]].
== Development of B cells ==<!-- This section is linked from [[Antibody]] -->
Immature B cells are produced in the [[bone marrow]] of most mammals. [[Rabbit]]s are an exception; their B cells develop in the [[appendix-sacculus rotundus]]. After reaching the IgM+ immature stage in the bone marrow, these transitional B cells migrate to the spleen where they mature into B lymphocytes[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&uid=17917068&cmd=showdetailview]. 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 light (L) and two heavy (H) chains, and the genes specifying them are found in the 'H' chain [[Locus (genetics)|locus]] and the 'L' chain [[Locus (genetics)|locus]]. In the H chain loci there are three regions, 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 L chain locus except there are only two regions, namely V and J. The list below describes the process of immunoglobulin formation at the different stages of B cell development.
* [[Progenitor B cells]] - Contains [[Germline]] H genes, Germline L genes
* Early Pro-B cells - undergoes D-J rearrangement on the H chains
* Late Pro-B cells - undergoes V-DJ rearrangement on the H chains
* Large Pre-B cells - the H chain is VDJ rearranged, Germline L genes
* Small Pre-B cells - undergoes V-J rearrangement on the L chains
* Immature B cells - VJ rearranged on L chains, VDJ rearranged on H chains. There is start of expression of IgM receptors.
* Mature B cells - There is start of expression of IgD
When the B cell fails in any step of the maturation process, it will die by a mechanism called [[apoptosis]], here called [[clonal deletion]].<ref>Parham, P. (2005). ''The Immune System,'' Garland Science Publishing, New York, NY.</ref> If it recognizes [[self-antigen]] during the maturation process, the B cell will become suppressed (known as [[anergy]]) or undergo apoptosis (also termed [[negative selection]]). B cells are continuously produced in the bone marrow, but only a small portion of newly made B cells survive to participate in the long-lived peripheral B cell pool.
B cell membrane receptors on which drugs may be active evolve during the B cell life span [http://www.healthvalue.net/Hyperactive_Blymphocytes_lifespan_receptors.html]. CD20 is present on preB cells, but disappears in mature B cells. TACI, BCMA and BAFF-R are present on immature B cells and mature B cells. The agonist of these 3 receptors is inhibited by [[Belimumab]].
==Functions==
The human body makes millions of different types of B cells each day that circulate in the [[blood]] and [[lymph]] 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 cell]]s and [[memory B cell]]s). 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 [[somatic hypermutation|hypermutate]] the variable region of its [[immunoglobulin]] [[gene]] ("somatic hypermutation") and possibly undergo [[class switching]].
===Clonality of B cells===
B cell exist as [[clone (cell biology)|clones]], meaning, all the B cells derived from a particular cell, and thus, the antibodies their differentiated progenies (see below) produce can recognize and/or bind the same components ([[epitope]]) of a given antigen. This has important consequences, most notably, the phenomenon of immunogenic memory relies on this clonality of B cells. The great diversity in immune response comes about because there are up to 10<sup>9</sup> clones with that many specificities for recognizing antigens. A single B cell or a clone of cells with shared specificity upon encountering its specific antigen (rather, the epitope), divides many times to produce many B cells, most of which differentiate into Plasma cells that can secrete antibodies into blood that bind the same epitope that elicited proliferation in the first place, while a very small minority survive as ''memory cells'' that can again recognize only the same epitope, and when that happens would divide further to produce more plasma and memory cells. However, with each such cycle, the number of surviving memory cells '''increases'''. This also is accompanied by ''affinity maturation'' that increases the sum total of epitopes that can be recognized by the related clones through random mutations in the epitope binding (and recognizing) portions of these cell. This subsequent amplification with improved specificity of immune response is known as ''secondary immune response''. If the cell that encountered the epitope to subsequently proliferate did so for the first time, it would be known as a ''naive'' cell, i.e., neither it nor any of its predecessors ever encountered this epitope.
===B cell types===
[[Image:Plasmacell.jpg|thumb|250px|right|A plasma cell]]
*'''[[Plasma B cell]]s''' (also known as ''plasma cells'') are large B cells that have been exposed to antigen and are producing and secreting large amounts of [[antibody|antibodies]], which assist in the destruction of [[microbe]]s by binding to them and making them easier targets for [[phagocyte]]s 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 cell]]s''' 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 cell]]s''' express IgM in greater quantities than IgG and its receptors show polyspecificity, meaning that they have low affinities for many different antigens, but 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.<ref>
{{cite journal
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| first =Encarnacion''
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| coauthors =Kenneth Dorshkind
| title =''New perspectives in B-1 B cell development and function''
| journal =[http://www.sciencedirect.com/science/journal/14714906 Trends in Immunology]
| volume =27
| issue =9
| pages =428–433
| publisher =Elsevier B.V.
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| doi =10.1016/j.it.2006.07.005}}
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| accessdate =2008-05-05
| doi_brokendate =2008-06-28 }}
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| authorlink =James W Tung''
| coauthors =Leonore A Herzenberg''
| title ="Unraveling B-1 progenitors"
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| id =
| accessdate =2008-05
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</ref>
*'''[[B-2 cell]]s''' are the conventional B cells most texts refer to.
==Recognition of antigen by B cells==
A critical difference between B cells and [[T cells]] is how each lymphocyte "sees" 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 [[Major histocompatibility complex|MHC]] molecule to the [[T cell receptor]].
[[Image:B cell activation.png|300px|left|thumb|Mechanism of action.]]
==Activation of B cells==<!-- This section is linked from [[Antibody]] -->
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 cell]]s).
B cells that have not been exposed to antigen, also known as ''Naive B cells'', can be activated in a T-cell dependent or independent manner.
===T-cell dependent activation===
When a macrophage ingests a [[pathogen]], it attaches parts of the pathogen's proteins to a [[major histocompatibility complex|class II MHC]] protein. This complex is moved to the outside of the cell membrane, where the [[epitope]] on the antigen can be recognized by a [[T cell]], which is compatible with similar structures on the cell membrane of a B cell. If the B cell and T cell structures match, the T cell will activate the B cell, which starts producing antibodies in large scale against the bits of pathogen, called antigen, it has found with its B cell receptor (a membrane bound antibody). Since, many clones of B memory/naive cells can recognize the same antigen, the response is [[polyclonal response|polyclonal]].
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 T<sub>h</sub>'' cell, the T cell secretes [[cytokine]]s 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 can no longer make the earlier isotypes, [[IgM]] or [[IgD]].
===T-cell independent activation===
Many antigens are T-independent, meaning they can deliver both of the signals to the B cell. [[mouse|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. There are two types of T-cell independent activation; ''Type 1 T cell-independent'' ([[polyclonal antibodies|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).
==The ancestral roots of B cells==
[[Image:Phagocytic B-cell NI.gif|thumb|right]]
In an October 2006 issue of [[Nature Immunology]], it was reported that certain B-cells of primitive [[vertebrates]] (like [[fish]] and [[amphibian]]s) are capable of [[phagocytosis]], a function usually associated with cells of the [[innate immune system]]. The authors of this article 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]]<ref>{{cite journal | author = J. Li, D.R. Barreda, Y.-A. Zhang, H. Boshra, A.E. Gelman, S. LaPatra, L. Tort & J.O. Sunyer | title = B lymphocytes from early vertebrates have potent phagocytic and microbicidal abilities | journal = Nature Immunology |year = 2006 | volume = 7 |pages = 1116–1124 |pmid=16980980 | doi = 10.1038/ni1389}}</ref>.
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.
==Origin of the word B cell==
The abbreviation "B" in B cell originally came from [[bursa of Fabricius|'''B'''ursa of Fabricius]], an organ in birds in which avian B [[cell (biology)|cells]] mature.<ref>[http://www.nlm.nih.gov/cgi/mesh/2007/MB_cgi?mode=&term=Bursa+of+Fabricius&field=entry Bursa]</ref> 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.
== Additional image ==
[[Image:Stimulation of specific clone of B cells and its proliferation.PNG|thumb|200px|center|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.<ref>{{cite book
| last = Goldsby
| first = Richard
| authorlink =
| coauthors = Kindt, TJ; Osborne, BA; Janis Kuby
| title = ''Immunology'' Fifth Edition
| publisher = W. H. Freeman and Company
| date = 2003
| location = New York
| pages = 119-120
| url =
| doi =
| id =
| isbn = 0-07167-4947-5}}</ref>]]
==See also==
*[[Affinity maturation]]
*[[Antibody]]
*[[Clonal selection]]
*[[Original antigenic sin]]
==References==
{{reflist}}
==External links==
* {{MeshNumber|A11.063.438|B-Lymphocytes}}
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