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. Usin...

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Bibliographic Details
Published in:The Journal of experimental medicine 2007-09, Vol.204 (9), p.2103-2114
Main Authors: Anderson, Shannon M, Tomayko, Mary M, Ahuja, Anupama, Haberman, Ann M, Shlomchik, Mark J
Format: Article
Language:English
Subjects:
Animals
B-Lymphocytes - cytology
B-Lymphocytes - immunology
B7-1 Antigen - immunology
Base Sequence
Biomarkers - metabolism
Bromodeoxyuridine - metabolism
Cell Survival
DNA - biosynthesis
Immunity, Cellular
Immunization
Immunologic Memory - immunology
Lymphocyte Subsets - cytology
Lymphocyte Subsets - immunology
Mice
Mice, Transgenic
Mutation - genetics
Receptors, Complement 3b - immunology
Selection, Genetic
Spleen - cytology
Time Factors
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Summary: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.
ISSN:0022-1007
1540-9538
1892-1007
DOI:10.1084/jem.20062571