Optimal Germinal Center Responses Require a Multistage T Cell:B Cell Adhesion Process Involving Integrins, SLAM-Associated Protein, and CD84

Jennifer L. Cannons, Hai Qi, Kristina T. Lu, Mala Dutta, Julio Gomez-Rodriguez, Jun Cheng, Edward K. Wakeland, Ronald N. Germain, Pamela L. Schwartzberg

Research output: Contribution to journalArticle

255 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)253-265
Number of pages13
JournalImmunity
Volume32
Issue number2
DOIs
StatePublished - Feb 26 2010

Keywords

  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Cannons, J. L., Qi, H., Lu, K. T., Dutta, M., Gomez-Rodriguez, J., Cheng, J., Wakeland, E. K., Germain, R. N., & Schwartzberg, P. L. (2010). Optimal Germinal Center Responses Require a Multistage T Cell:B Cell Adhesion Process Involving Integrins, SLAM-Associated Protein, and CD84. Immunity, 32(2), 253-265. https://doi.org/10.1016/j.immuni.2010.01.010