B cells alter the phenotype and function of follicular-homing CXCR5+ T cells.
The CXC chemokine receptor (CXCR)5 is rapidly induced on activated CD4(+) T cells, allowing migration toward secondary lymphoid tissue follicles, where the CXCR5 ligand CXCL13/BCA-1 is produced. Such CXCR5(+) T cells provide efficient help for B cell immunoglobulin production and are termed follicular B helper T (T(FH)) cells. However, the molecular mechanisms by which T(FH) cells provide B cell help are unknown. Here, we demonstrate that newly generated (antigen-primed) T(FH) cells express a phenotype consistent with induction of B cell proliferation, but co-culture with primed B cells resulted in a switch to a plasma cell-inducing phenotype, characterized by loss of CD154, induction of CD70 and an increase in IL-10 production capacity. The ability to produce IL-10 could be maintained as a stable phenotype, but its secretion was strictly dependent on inducible costimulator (ICOS) signaling. Furthermore, B cells preserved a lymph node migration phenotype in proliferating T(FH) cells by preventing the loss of CC chemokine receptor (CCR)7 and the induction of CCR5. Thus, B cells directly modulate the B cell helper phenotype in T(FH) cells and actively promote their prolonged co-localization with these cells.
Ebert
Lisa M
LM
Theodor-Kocher Institute, University of Bern, Bern, Switzerland. lisa.ebert@tki.unibe.ch
Horn
Michael P
MP
Lang
Alois B
AB
Moser
Bernhard
B
D000917:Antibody Formation / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine / Q000276:immunology; D018121:Receptors, Cytokine / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D000945:Antigens, Differentiation, T-Lymphocyte; C095085:CXCR5 protein, human; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D016753:Interleukin-10