Molecular programming of B cell memory.

Department of Immunology and Microbial Sciences, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Nature Reviews Immunology (Impact Factor: 33.84). 12/2011; 12(1):24-34. DOI: 10.1038/nri3128
Source: PubMed

ABSTRACT The development of high-affinity B cell memory is regulated through three separable phases, each involving antigen recognition by specific B cells and cognate T helper cells. Initially, antigen-primed B cells require cognate T cell help to gain entry into the germinal centre pathway to memory. Once in the germinal centre, B cells with variant B cell receptors must access antigens and present them to germinal centre T helper cells to enter long-lived memory B cell compartments. Following antigen recall, memory B cells require T cell help to proliferate and differentiate into plasma cells. A recent surge of information - resulting from dynamic B cell imaging in vivo and the elucidation of T follicular helper cell programmes - has reshaped the conceptual landscape surrounding the generation of memory B cells. In this Review, we integrate this new information about each phase of antigen-specific B cell development to describe the newly unravelled molecular dynamics of memory B cell programming.

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    ABSTRACT: Germinal centers (GCs) are specialized environments in which B cells mutate their BCR to identify new Abs with high affinity to a challenging Ag. B cells are selected in an evolutionary process of multiple rounds of mutation and selection. In the past decade, mechanisms of B cell migration, division, mutation, selection, and final differentiation have been extensively studied. Thereby, modulations of these mechanisms either optimize the quality, in terms of affinity, or the quantity of generated Abs, but never both, leading to an unclear effect on the overall efficiency of the Ab response. In this article, we predict with mathematical models that an affinity-dependent number of GC B cell divisions overcomes the dichotomy of quality and quantity, and has to be considered as a good target for immune interventions, in particular, in the elderly population with poor GC responses.
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