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.

CD27 Instructs CD4+ T Cells to Provide Help for the Memory CD8+ T Cell Response after Protein Immunization

“…It is clear from studies in CD27 Ϫ/Ϫ and CD70 transgenic mice that CD27/CD70 interactions can promote CD4 ϩ effector T cell accumulation, most evidently in the lung after influenza virus infection (23,26). In the same virus infection model, as well as after protein immunization, CD27 deficiency did not affect the B cell response (27). These findings suggest a role for CD27 on CD4 ϩ T cells in CD8 ϩ T cell rather than B cell help.…”

“…Studies in CD27 Ϫ/Ϫ and CD70 transgenic mice have already indicated that CD27/CD70 interactions affect accumulation of CD4 ϩ T cell effector cells in lymphoid organs and tissue sites (23,26). However, CD27/CD70 interactions do not contribute to the B cell response after virus infection or protein immunization (24,27,36), indicating that CD27 on CD4 ϩ T cells is not important for B cell help, at least in the mouse. Our present findings demonstrate that CD27 contributes to the capacity of CD4 ϩ T cells to deliver CD8 ϩ T cell help.…”

Unchecked CD70 Expression on T Cells Lowers Threshold for T Cell Activation in Rheumatoid Arthritis

“…An important role for CD27 stimulation has also been documented for the expansion of effector T cells and the accumulation of CD8 ϩ effector T cells at the site of infection (35,36). Stimulation of CD27 on primed B cells plays a role in the expansion of centroblasts and, at least in humans, promotion of plasma cell differentiation (37,38). CD27 signals through TNFR-associated factor-2/5 and NF-B-inducing kinase, leading to the activation of the NF-B and c-Jun kinase pathways and promoting cell survival and differentiation (39).…”

Roles of TRAF molecules in B lymphocyte function

“…In the human, CD27 is expressed on B cells following stimulation through the B cell antigen-receptor [33] and is expressed by memory B cells [34]. In the mouse, CD27 expression is extremely transient and exists only on centroblasts and on a very low frequency of memory B cells [35]. Data from the CD27 deficient mouse reveal that CD27 appears to have only a minor role in germinal center formation [35].…”

“…In the mouse, CD27 expression is extremely transient and exists only on centroblasts and on a very low frequency of memory B cells [35]. Data from the CD27 deficient mouse reveal that CD27 appears to have only a minor role in germinal center formation [35]. Other experiments in this mouse demonstrated that in the mouse, CD27 is more important in the generation of effector and memory T cells [36,37].…”