1998
DOI: 10.1111/j.1600-065x.1998.tb01441.x
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The roles of antibody variable region hypermutation and selection in the development of the memory B‐cell compartment

Abstract: Somatic hypermutation and selection of immunoglobulin (Ig) variable (V)-region genes, working in concert, appear to be essential for memory B-cell development in mammals. There has been substantial progress on the nature of the cis-acting DNA elements that regulate hypermutation. The data obtained suggest that the mechanisms of Ig gene hypermutation and transcription are intimately intertwined. While it has long been appreciated that stringent phenotypic selection forces are imposed on the somatically mutated … Show more

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Cited by 37 publications
(40 citation statements)
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“…Upon encountering cognate Ag, B cells can become activated and mature into isotypeswitched short-lived plasma cells (PCs) at extrafollicular sites to generate primary Ab responses to either T cell-independent or T cell-dependent (TD) Ags (1,2). In response to TD Ags, B cells can also form germinal centers (GCs) in the primary follicle with CD4 + T follicular helper (TFH) cells and follicular dendritic cells (3)(4)(5)(6). B cells undergo a dynamic selection process in the GCs, during which they somatically mutate their Ig V region genes to generate high-affinity memory B cells and long-lived PCs that give rise to long-term serum Ab titers (3)(4)(5)(6).…”
Section: T He Development Of Ab Responses Occurs In Distinct Stagesmentioning
confidence: 99%
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“…Upon encountering cognate Ag, B cells can become activated and mature into isotypeswitched short-lived plasma cells (PCs) at extrafollicular sites to generate primary Ab responses to either T cell-independent or T cell-dependent (TD) Ags (1,2). In response to TD Ags, B cells can also form germinal centers (GCs) in the primary follicle with CD4 + T follicular helper (TFH) cells and follicular dendritic cells (3)(4)(5)(6). B cells undergo a dynamic selection process in the GCs, during which they somatically mutate their Ig V region genes to generate high-affinity memory B cells and long-lived PCs that give rise to long-term serum Ab titers (3)(4)(5)(6).…”
Section: T He Development Of Ab Responses Occurs In Distinct Stagesmentioning
confidence: 99%
“…In response to TD Ags, B cells can also form germinal centers (GCs) in the primary follicle with CD4 + T follicular helper (TFH) cells and follicular dendritic cells (3)(4)(5)(6). B cells undergo a dynamic selection process in the GCs, during which they somatically mutate their Ig V region genes to generate high-affinity memory B cells and long-lived PCs that give rise to long-term serum Ab titers (3)(4)(5)(6). The B cell memory response, characterized by the formation of long-lived PCs and quiescent memory B cells, is an important component of protective immunity to bacterial and viral pathogens (7,8).…”
Section: T He Development Of Ab Responses Occurs In Distinct Stagesmentioning
confidence: 99%
“…There is good evidence that signals transmitted both via the BCR and from CD4 ϩ T cells are required for memory B cell formation (1)(2)(3). The generation of optimal memory B cell responses to foreign Ags also requires activation of the innate immune system, either by pathogens (e.g., via TLRs) or with adjuvants (4).…”
mentioning
confidence: 99%
“…Once in the GC microenvironment, V gene hypermutation, combined with stringent clonal selection processes, might result in the emergence of mutant derivatives of the founding, autoreactive clones that had lost affinity for autoantigen, resulting in expression of high levels of sBCR, proficient Ag capture, processing, and presentation to GC T cells, and induction of memory cells and secondary AFCs. Such a process of "specificity maturation" (89,90) might also facilitate the nucleation of the GC response by ensuring that not all B cells are driven to terminal differentiation during the initial stages of a TD immune response. We are presently testing these ideas by determining whether canonical R55 B cells exclusively enter the GC response after Ars immunization in vivo, and whether hypermutated progeny of this clonotype can contribute to the anamnestic AFC response and give rise to memory B cells expressing high levels of sBCR.…”
Section: Discussionmentioning
confidence: 99%