MHC-Restricted B-Cell Antigen Presentation in Memory B-Cell Maintenance and Differentiation

Abstract

Memory B-cell development, maintenance, and differentiation have been believed to be tightly regulated by T cells through major histocompatibility complex (MHC)-II-restricted cognate interaction. However, recent studies have indicated that memory B cells are a heterogeneous population with various ontogeny and with derivations from T-cell-independent as well as T-cell-dependent response. In addition, several studies highlight T-cell-independent maintenance and differentiation of memory B cells by innate polyclonal stimuli associated with Toll-like-receptors (TLRs). Thus, both T-cell-dependent and T-cell-independent mechanisms with possibly different physiological functions are required for maximal memory B-cell maintenance and differentiation. In this review, we discuss the mechanisms of memory B-cell maintenance and differentiation by re-examining the requirement for MHC-II-restricted B-cell antigen presentation based on our recent study in a mouse model that lacks MHC-II on memory B cells. We propose that MHC-II-restricted memory B-cell maintenance and differentiation are the indispensable mechanisms by which we achieve health and the maximum quality of memory response with specific antibody production, while preventing plasma cell differentiation from self-reactive memory B cells under the control of T-helper cells and possibly regulatory T cells.