title: Pivotal advance: CD45RB glycosylation is specifically regulated during human peripheral B cell differentiation.
abstract: A screen of cell surface markers differentially expressed during peripheral B cell differentiation identified that the CD45RB epitope detected by the mAb MEM-55 was highly expressed on CD27(+) memory B cells and absent on CD27(-) naïve B cells. IgG(+)CD27(-) memory and a previously unacknowledged CD27(-) population in blood also expressed high levels of CD45RB(MEM55). Naïve and memory B cells from tonsils followed the pattern observed in blood, and CD38(high) B cells had a bimodal expression pattern when analyzed using flow cytometry. No CD38(high) GC B cells, however, expressed the CD45RB(MEM55) epitope when assayed using immunohistochemistry. Rather, CD38(high)CD45RB(MEM55high) B cells had a distinct cellular phenotype and were localized outside of GCs. CD45RB epitopes, detected by other antibody clones, were expressed at high levels through B cell differentiation, and no changes in splicing of the CD45RB exon were observed during B cell differentiation. Instead, B cells regulated their expression of the CD45RB(MEM55) epitope through site-specific modifications of an O-linked glycochain. CD4(+) T cells differentially spliced CD45 but did not vary the glycosylation of the CD45RB(MEM55) epitope, and CD8(+) cells modified CD45RB(MEM55) expression in a similar manner as B cells. Monocytes expressed the CD45RB exon but not the CD45RB(MEM55) epitope. As CD45 is a highly expressed tyrosine phosphatase that regulates antigen receptor signaling strength in lymphocytes, we conclude that regulated O-linked glycosylation of CD45RB can be used to follow B cell differentiation and that this regulation may be involved in fine-tuning antigen signaling in the cell.
authors.affiliation: University of Gothenburg, SE 405 30 Gothenburg, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Koethe
authors.forename: Linda
authors.initials: L
authors.lastname: Zander
authors.forename: Sofia
authors.initials: S
authors.lastname: Köster
authors.forename: Adelaide
authors.initials: A
authors.lastname: Annan
authors.forename: Anders
authors.initials: A
authors.lastname: Ebenfelt
authors.forename: Jo
authors.initials: J
authors.lastname: Spencer
authors.forename: Mats
authors.initials: M
authors.lastname: Bemark
mesh_terms: D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology*; D002469:Cell Separation; D005434:Flow Cytometry; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D007156:Immunologic Memory / Q000276:immunology; D047468:Immunoprecipitation; D017493:Leukocyte Common Antigens / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D015398:Signal Transduction
chemical_list: D017493:Leukocyte Common Antigens