New markers for murine memory B cells that define mutated and unmutated subsets.
The study of murine memory B cells has been limited by small cell numbers and the lack of a definitive marker. We have addressed some of these difficulties with hapten-specific transgenic (Tg) mouse models that yield relatively large numbers of antigen-specific memory B cells upon immunization. Using these models, along with a 5-bromo-2'-deoxyuridine (BrdU) pulse-label strategy, we compared memory cells to their naive precursors in a comprehensive flow cytometric survey, thus revealing several new murine memory B cell markers. Most interestingly, memory cells were phenotypically heterogeneous. Particularly surprising was the finding of an unmutated memory B cell subset identified by the expression of CD80 and CD35. We confirmed these findings in an analogous V region knock-in mouse and/or in non-Tg mice. There also was anatomic heterogeneity, with BrdU(+) memory cells residing not just in the marginal zone, as had been thought, but also in splenic follicles. These studies impact the current understanding of murine memory B cells by identifying new phenotypes and by challenging assumptions about the location and V region mutation status of memory cells. The apparent heterogeneity in the memory compartment implies either different origins and/or different functions, which we discuss.
Anderson
Shannon M
SM
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Tomayko
Mary M
MM
Ahuja
Anupama
A
Haberman
Ann M
AM
Shlomchik
Mark J
MJ
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology; D001483:Base Sequence; D015415:Biomarkers / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002470:Cell Survival; D004247:DNA / Q000096:biosynthesis; D007111:Immunity, Cellular; D007114:Immunization; D007156:Immunologic Memory / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D017463:Receptors, Complement 3b / Q000276:immunology; D012641:Selection, Genetic; D013154:Spleen / Q000166:cytology; D013997:Time Factors
D018122:B7-1 Antigen; D015415:Biomarkers; D017463:Receptors, Complement 3b; D004247:DNA; D001973:Bromodeoxyuridine
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