Original Article

Antigen-specific B Cell Memory: Expression and Replenishment of a Novel B220^- Memory B Cell Compartment

Correspondence to: Michael G. McHeyzer-Williams, Duke University Medical Center, Jones Bldg., Rm. 316, Box 3010, Research Dr., Durham, NC 27710. Tel:919-613-7821 Fax:919-684-8982 E-mail:mchey002{at}duke.edu.

The mechanisms that regulate B cell memory and the rapid recall response to antigen remain poorly defined. This study focuses on the rapid expression of B cell memory upon antigen recall in vivo, and the replenishment of quiescent B cell memory that follows. Based on expression of CD138 and B220, we reveal a unique and major subtype of antigen-specific memory B cells (B220^-CD138^-) that are distinct from antibody-secreting B cells (B220^+/-CD138⁺) and B220⁺CD138^- memory B cells. These nonsecreting somatically mutated B220^- memory responders rapidly dominate the splenic response and comprise >95% of antigen-specific memory B cells that migrate to the bone marrow. By day 42 after recall, the predominant quiescent memory B cell population in the spleen (75–85%) and the bone marrow (>95%) expresses the B220^- phenotype. Upon adoptive transfer, B220^- memory B cells proliferate to a lesser degree but produce greater amounts of antibody than their B220⁺ counterparts. The pattern of cellular differentiation after transfer indicates that B220^- memory B cells act as stable self-replenishing intermediates that arise from B220⁺ memory B cells and produce antibody-secreting cells on rechallenge with antigen. Cell surface phenotype and Ig isotype expression divide the B220^- compartment into two main subsets with distinct patterns of integrin and coreceptor expression. Thus, we identify new cellular components of B cell memory and propose a model for long-term protective immunity that is regulated by a complex balance of committed memory B cells with subspecialized immune function.

Key Words: antigen-specific immunity, immunological memory, B lymphocyte memory, B lymphocyte subset, mice

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