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Original Article

Louise J. McHeyzer-Williams^a, Melinda Cool^a, and Michael G. McHeyzer-Williams^a

^a Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710
Duke University Medical Center, Jones Bldg., Rm. 316, Box 3010, Research Dr., Durham, NC 27710.919-684-8982919-613-7821

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

© 2000 The Rockefeller University Press

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