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The Journal of Immunology, 2006, 176: 4706-4715.
Copyright © 2006 by The American Association of Immunologists

Identification of Memory B Cells Using a Novel Transgenic Mouse Model1

Craig P. Chappell and Joshy Jacob2

Department of Microbiology and Immunology, Emory Vaccine Center, Emory University, Atlanta, GA 30307

Memory B cells help to protect the host from invading pathogens by maintaining persistent levels of Ag-specific serum Ab and generating rapid Ab responses upon re-exposure to Ag. Unambiguous identification of memory B cells has been a major obstacle to furthering our knowledge concerning both the development of B cell memory and secondary Ab responses due to an absence of specific cell surface markers. Germinal centers (GCs) are thought to be the major site of Ig hypermutation and Ag-driven selection of memory B cells. To develop a model that would identify GC-derived memory B cells, we generated transgenic mice that expressed cre recombinase in a GC-specific fashion. Interbreeding these mice with the cre-reporter strain, ROSA26R, produced progeny in which beta-galactosidase (beta-gal) was permanently expressed in B cells of the GC-memory pathway. Analysis following immunization with (4-hydroxy-3-nitrophenyl)acetyl coupled to chicken {gamma} globulin showed that long-lived beta-gal+ B cells exclusively contained somatically mutated {lambda}1 V regions and were capable of producing Ag-specific Ab-forming cell (AFC) responses that were >100-fold higher than those afforded by beta-gal B cells following adoptive transfer to naive hosts. Secondary challenge of immune mice showed that only ~20% of secondary AFCs expressed beta-gal. Interestingly, we found that somatic hypermutation of rearranged {lambda}1 V regions within secondary AFCs showed a strong correlation with beta-gal expression, suggesting that nonmutated B cells contribute significantly to secondary Ab responses. This model should provide useful insights into memory B cell development, maintenance, and differentiation following immunization or pathogenic infection.


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The JI 2006 176: 4507-4508. [Full Text]  



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