TY - JOUR
T1 - Optimal Germinal Center Responses Require a Multistage T Cell:B Cell Adhesion Process Involving Integrins, SLAM-Associated Protein, and CD84
AU - Cannons, Jennifer L.
AU - Qi, Hai
AU - Lu, Kristina T.
AU - Dutta, Mala
AU - Gomez-Rodriguez, Julio
AU - Cheng, Jun
AU - Wakeland, Edward K.
AU - Germain, Ronald N.
AU - Schwartzberg, Pamela L.
N1 - Funding Information:
We thank R. Handon and A. Venegas for invaluable technical assistance; M. Kirby and S. Anderson for cell sorting; J. Fekecs for graphics assistance; and K. Nichols and S.-H. Hwang for mouse reagents. This work was funded by the intramural research programs of the NHGRI and NIAID, NIH, USA.
PY - 2010/2/26
Y1 - 2010/2/26
N2 - 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.
AB - 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.
KW - MOLIMMUNO
UR - http://www.scopus.com/inward/record.url?scp=76949091588&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=76949091588&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2010.01.010
DO - 10.1016/j.immuni.2010.01.010
M3 - Article
C2 - 20153220
AN - SCOPUS:76949091588
SN - 1074-7613
VL - 32
SP - 253
EP - 265
JO - Immunity
JF - Immunity
IS - 2
ER -