Optimal germinal center responses require a multistage T cell:B cell adhesion process involving integrins, SLAM-associated protein, and CD84.
CD4(+) T cells deficient in signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) exhibit a selective impairment in adhesion to antigen-presenting B cells but not dendritic cells (DCs), resulting in defective germinal center formation. However, the nature of this selective adhesion defect remained unclear. We found that whereas T cell:DC interactions were primarily integrin dependent, T cell:B cell interactions had both an early integrin-dependent phase and a sustained phase that also required SAP. We further found that the SLAM family member CD84 was required for prolonged T cell:B cell contact, optimal T follicular helper function, and germinal center formation in vivo. Moreover, both CD84 and another SLAM member, Ly108, mediated T cell adhesion and participated in stable T cell:B cell interactions in vitro. Our results reveal insight into the dynamic regulation of T cell:B cell interactions and identify SLAM family members as critical components of sustained T cell:B cell adhesion required for productive humoral immunity.
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Jennifer L
JL
Cannons
Hai
H
Qi
Kristina T
KT
Lu
Mala
M
Dutta
Julio
J
Gomez-Rodriguez
Jun
J
Cheng
Edward K
EK
Wakeland
Ronald N
RN
Germain
Pamela L
PL
Schwartzberg
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000950:Antigens, Ly / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018858:Germinal Center / Q000378:metabolism* / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000098546:Interleukin-21
D015703:Antigens, CD; D000950:Antigens, Ly; D007371:Interferon-gamma; D007378:Interleukins; D047908:Intracellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; D000071179:Signaling Lymphocytic Activation Molecule Associated Protein; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D000098546:Interleukin-21; C498971:Cd84 protein, mouse; C000604060:SLAMF6 protein, human; C499569:Sh2d1a protein, mouse; C000604063:Slamf6 protein, mouse