Human CD57+ germinal center-T cells are the major helpers for GC-B cells and induce class switch recombination

We demonstrated that CD57+ GC-Th cells are highly efficient in helping B cell production of all four subsets of Ig (IgM, IgG, IgA and IgE) compared to other T-helper cells located in germinal centers or interfollicular areas. CD57+ GC-Th cells were particularly more efficient than other T cells in helping GC-B cells but not na？ve B cells. CD57+ GC-Th cells induced the expression of activation-induced cytosine deaminase (AID) and class switch recombination in developing B cells. IgG1-3 and IgA1 were the major Ig isotypes induced by CD57+ GC-Th cells. CD40L, but not IL-4, IL-10 and IFN-γ, was critical in CD57+ GC-Th cell-driven B cell production of Ig. However, IL-10, when added exogenously, significantly enhanced the helper activity of CD57+ GC-Th cells, while TGF-β1 completely and IFN-γ partially suppressed the CD57+ GC-Th cell-driven Ig production.CD57+CD4+ T cells in the germinal centers of human lymphoid tissues are the major T helper cell subset for GC-B cells in Ig synthesis. Their helper activity is consistent with their capacity to induce AID and class switch recombination, and can be regulated by CD40L, IL-4, IL-10 and TGF-β.In germinal centers (GC), B cells undergo clonal expansion, somatic hyper-mutation in the variable region of antibody genes [1-3] and class switch recombination (CSR) from IgM to IgG, IgA, and IgE [4-8], processes that are dependent on helper T cells [9-11]. Antibodies to the CD57 epitope (HNK-1) have been used to identify a T cell type in germinal centers in human tonsils, spleen and lymph nodes. These cells are CD4+ T cells [12-14], exhibit a memory phenotype (CD45RO+CD45RA-) [15] and are not cytolytic [16]. CD57+ GC-Th cells proliferate only when they are TCR-activated in the presence of IL-2 [17,18]. CD57+ GC-Th cells express the B-cell zone homing chemokine receptor CXCR5 but not the T cell zone homing chemokine receptor CCR7, a pattern consistent with their specific localization in GC [19]. Based upon their non-polarized cytokine p