Class-switched marginal zone B cells in spleen have relatively low numbers of somatic mutations.
The vast majority of rodent splenic marginal zone (MZ)-B cells are naive IgM(+) cells. A small fraction of these MZ-B cells carry mutated V-genes, and represent IgM(+) memory MZ-B cells. Here we reveal further heterogeneity of B cells with a MZ-B cell phenotype, by providing evidence for the existence of class-switched memory MZ-B cells in the rat. In essence, we observed IGHV5 encoded Cγ transcripts, among FACS-purified MZ-B cells, defined as HIS24(low)HIS57(bright) cells. Furthermore, we found that most IgG encoding transcripts are mutated. There is no significant difference in IGHV5 repertoire and subclass usage of these IgG encoding transcripts collected from B cells with a MZ-B cell phenotype and B cells with a follicular (FO) B cell phenotype. However, the IGHV5 genes encoding for IgG antibodies of MZ-B cells exhibited significantly fewer mutations, compared to those with a FO-B cell phenotype. In one rat we found a clonally related set of IgG encoding sequences, of which one was derived from the MZ-B cell fraction and the other from the FO-B cell fraction. We speculate that these two subpopulations of class-switched B cells are both descendants from naive FO-B cells and are generated in germinal centers. Class-switched memory cells with a MZ-B cell phenotype may provide the animal with a population of IgG memory cells that can respond rapidly to blood-borne pathogens.
Department of Cell Biology, Immunology Section, University Medical Center Groningen, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands.
Jacobus
J
Hendricks
Annie
A
Visser
Peter M
PM
Dammers
Johannes G M
JG
Burgerhof
Nicolaas A
NA
Bos
Frans G M
FG
Kroese
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002458:Cell Fractionation; D002999:Clone Cells; D005786:Gene Expression Regulation; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020539:Sequence Analysis, Protein; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D013154:Spleen / Q000166:cytology* / Q000276:immunology*
D000941:Antigens; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D012333:RNA, Messenger