Follicular helper T cell differentiation requires continuous antigen presentation that is independent of unique B cell signaling.
Effective humoral immunity depends on the support of B cell responses by T follicular helper (Tfh) cells. Although it has been proposed that Tfh cell differentiation requires T-B interactions, the relative contribution of specific populations of Ag-presenting cells remains unknown. We employed three independent strategies that compromised interactions between CD4(+) T cells and activated B cells in vivo. Whereas the expansion of CD4(+) T cells was relatively unaffected, Tfh cell differentiation was completely blocked in all scenarios. Surprisingly, augmenting antigen presentation by non-B cells rescued Tfh cell differentiation, as determined by surface phenotype, gene expression, and germinal center localization. We conclude that although Ag presentation by responding B cells is typically required for the generation of Tfh cells, this does not result from the provision of a unique B cell-derived signal, but rather because responding B cells rapidly become the primary source of antigen.
Deenick
Elissa K
EK
Immunology Program, Garvan Institute of Medical Research, Darlinghurst, 2010, NSW, Australia. e.deenick@garvan.org.au
Chan
Anna
A
Ma
Cindy S
CS
Gatto
Dominique
D
Schwartzberg
Pamela L
PL
Brink
Robert
R
Tangye
Stuart G
SG
D000818:Animals; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D051560:Proto-Oncogene Proteins c-bcl-6 / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology*
D019013:CD40 Antigens; D047908:Intracellular Signaling Peptides and Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; C499569:Sh2d1a protein, mouse; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein