IgM memory B cells: specific effectors of innate-like and adaptive responses

Abstract

Antigen-experienced IgM⁺ B cells with mutated V genes have emerged as important effectors of both adaptive and innate-like immune responses. While their precise role in recall responses appear to differ according to the nature of the immunogen or the infectious agent, they are able to achieve rapid plasma cell differentiation, germinal center re-initiation, as well as IgM and IgG memory pool replenishment, which establishes them as multi-lineage precursors of the various functional memory subsets. For innate-like responses, recent data have shown that activation by gut commensals is able to generate, both in mice and humans, a systemic IgM⁺ population with specificity against glycan epitopes, which displays broad cross-reactivity towards multiple micro-organisms, and ensures a first line of defense against systemic infections.

Figure 1. IgM memory B cells in mucosal and innate-like responses: recent advances.

This figure describes recent data that demonstrated linkage of systemic or circulating IgM⁺ B cells harboring mutated receptors with B cells diversifying in germinal centers from gut-associated lymphoid tissues. In the mouse (lower part), a splenic IgM memory population is shown to accumulate with time, generated by the constant output of chronic GC responses in Peyer's patches as well as from spontaneous splenic GC, triggered by antigens of endogenous or commensal origin (24,25). These splenic IgM memory B cells show cross-reactivity against glycan antigens of both commensal and infectious bacterial species. Such broad cross-reactivity is also observed in humans for clonally related anti-Klebsiella gut IgA plasmablasts and circulating IgM⁺ B cells with mutated Ig receptors (26). Also in humans (upper part), an IgM plasma cell subset, together with IgA, is generated from gut memory responses, while only IgA plasma cells are detected in the mouse gut (29). CD27⁺ IgA, IgM-only and MZ (IgM⁺IgD⁺) showed clonal relationships in blood, while, clonal relationships among gut memory B cells were restricted to the IgM-only/MZ and IgM-only/IgA subsets, as IgA and MZ B cells seem to lack such common clonal origin. All gut subsets showed some clonal relatedness with germinal center B cells (30). Whether MZ B cells in the spleen show similar relatedness with B cell populations diversifying against gut antigens remains to be determined.