title: CD27 is acquired by primed B cells at the centroblast stage and promotes germinal center formation.
abstract: Studies on human B cells have featured CD27 as a marker and mediator of the B cell response. We have studied CD27 expression and function on B cells in the mouse. We find that B cells acquire CD27 at the centroblast stage and lose it progressively upon further differentiation. It is not a marker for somatically mutated B cells and is present at very low frequency on memory B cells. Enrichment of CD27 among centroblasts and the presence of its ligand CD70 on occasional T and B cells in or near germinal centers (GCs) suggested a role for CD27/CD70 interactions in clonal B cell expansion. Accordingly, GC formation in response to influenza virus infection was delayed in CD27 knockout mice. CD27 deficiency did not affect somatic hypermutation or serum levels of virus-specific IgM, IgG, and IgA attained in primary and recall responses. Adoptive transfer of T and B cells into CD27/CD28(-/-) mice revealed that CD27 promotes GC formation and consequent IgG production by two distinct mechanisms. Stimulation of CD27 on B cells by CD28(+) Th cells accelerates GC formation, most likely by promoting centroblast expansion. In addition, CD27 on T cells can partially substitute for CD28 in supporting GC formation.
authors.affiliation: Division of Immunology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Xiao
authors.forename: Jenny
authors.initials: J
authors.lastname: Hendriks
authors.forename: Petra
authors.initials: P
authors.lastname: Langerak
authors.forename: Heinz
authors.initials: H
authors.lastname: Jacobs
authors.forename: Jannie
authors.initials: J
authors.lastname: Borst
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D018106:CD28 Antigens / Q000378:metabolism; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology; D007136:Immunoglobulins / Q000096:biosynthesis / Q000097:blood; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D018106:CD28 Antigens; D007136:Immunoglobulins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7