Subspecialization of CXCR5+ T cells:: B helper activity is focused in a germinal center-localized subset of CXCR5+ T cells

The T helper (Th) cell pool is composed of specialized cells with heterogeneous effector functions. Apart from Th1 and 2 cells, CXCR5(+) T cells have been suggested to be another type of effector T cell specialized for B cell help. We show here that CXCR5(+) T cells are heterogeneous and we identify subsets of CXCR5+ CD4 T cells that differ in function and microenvironmental localization m secondary lymphoid tissues. CD57(+)CXCR5 T cells, hereafter termed germinal center Th (GC-Th) cells, are localized only in GCs, lack CCR7, and are highly responsive to the follicular chemokine B lymphocyte chemoattractant but not to the T cell zone EBI1-ligand chemokine. Importantly, GC-Th cells are much more efficient than CD57(-)CXCR5(+) T cells or CXCR5(-) T cells in inducing antibody production from B cells. Consistent with their function, GC-Th cells produce elevated levels of interleukin 10 upon stimulation which, with other cytokines and costimulatory molecules, may help confer their B cell helper activity. Our results demonstrate that CXCR5(+) T cells are functionally heterogeneous and that the GC-Th cells, a small subset of CXCR5(+) T cells, are the key helpers for B cell differentiation and antibody production in lymphoid tissues.