> Immunological MemoryImmunological Memory
T-cell dependent antigen exposure leads to the formation of short-lived
antibody secreting plasma cells and germinal center (GC) B cells which
undergo somatic mutations and isotype switching. GC B cells are believed
to generate memory B cells and long-lived plasma cells under the antigen-
driven selection, however, to our knowledge, no direct evidence proves
Memory B cells show a unique morphology and phenotype and acquire several
intrinsic properties that differ from other B cell stages, such as longevity,
preferential localization in the antigen draining sites, and rapid response
to antigen reexposure by differentiating into plasma cells. However, the
mechanisms underlying memory B cell development, maintenance, and terminal
differentiation remain obscure.
Our intention is to ascertain the origin of memory B cells and the mechanisms
underlying memory B cell development, maintenance, and signaling responsible
for terminal differentiation. To approach these fundamental problems, we are
analyzing the dynamics of memory B cells by virtue of FACS with a seven color
system and characterizing the genes that are highly expressed in memory B cells.
We suggest that memory B cells are generated within 3 wk after immunization.
We observed that CD95(Fas) regulates the selection of the memory B cell
repertoire (Immunity 2001; see Fig.1); however, unfortunately, the underlying
mechanism remains obscure. We suggest that memory B cells are susceptible to
apoptosis at terminal differentiation, owing to their hyper-reactivity to
antigen reexposure, whereas a Ras-mediated cascade may rescue the cell death
(Immunity 2005; see Fig.1). These results support the view that memory B cells
have a unique signaling module, distinct from other B cell stages (see blow).
Finally regarding the pathway of memory B cell generation, our collaborative
work with Dr. Tokuhisaﾕs group at Chiba University have provided the possibility
memory B cells are generated at the early immune response, probably prior to the
generation of apoptosis susceptible germinal centers at terminal differentiation
(Immunity 2002, Int. Immunol. 2005).