Hétérogénéité et fonctions des lymphocytes B chez l’homme

Abstract

L’étude de l’expression de différents marqueurs membranaires permet de délimiter plusieurs sous-populations de lymphocytes B, qui jouent des rôles distincts dans la réponse immunitaire humorale. En outre, les lymphocytes B possèdent des fonctions indépendantes de la production d’anticorps. Produits tout au long de la vie par la moelle osseuse, où s’effectuent les réarrangements des gènes d’immunoglobulines au cours des étapes de maturation des précurseurs de la lignée B, les lymphocytes B naïfs co-expriment des IgM et des IgD membranaires (IgMlow IgDhigh) qui constituent leur récepteur pour l’antigène (BcR), et sont susceptibles de s’orienter vers différentes voies de différenciation conduisant à la mise en place de sous-populations distinctes.

B lymphocytes represent an important arm of the immune system. Besides their main function of providing antibodies protecting against pathogens, they also exert some regulatory functions, in particular for secondary lymphoid tissue differentiation. Human B cells can be divided in varioussubsets representing different maturation stages and different pathways of humoral immune responses. Naïve IgMlow IgDhigh CD27- B cells can participate in T-cell dependent immune responses leading to germinal center formation in follicles of secondary lymphoid organs. Interactions with follicular helper T cells, a recently identified CD185+ T cell population providing help to follicular B cell, involve costimulatory molecules including CD40, CD27, CD278 and SAP-recruiting receptors. B cell interaction with follicular helper T cells represents a critical step controlling the generation of plama cells that ultimately produce high affinity, somatically mutated, class-switched antibodies or of their memory B cell counterpart (identified as CD27+ Ig switched or IgMonly B cells). IgMhigh IgDlow CD27+ B cells are a puzzling population apparently specialized in T-independent responses to bacterial capsular polysaccharides. The extra-follicular, probably antigen-independent, differentiation pathway of these cells, allowing pre-immune repertoire diversification by somatic hypermutation, is not yet characterized. However, circulating IgMhigh IgDlow CD27+ B cells are similar to splenic marginal zone B cells. In addition to these subsets, minor populations can also be identified in peripheral blood, such as transitional B cells and plasma blasts. All together, deciphering human B cell heterogeneity provides tools for investigations of humoral immunodeficiencies and auto-immune diseases, that will in return shed more light on B cell biology.