The tetraspanin protein CD37 regulates IgA responses and antifungal immunity

PLoS Pathog. 2009 Mar;5(3):e1000338. Epub 2009 Mar 13. 

The tetraspanin protein CD37 regulates IgA responses and anti-fungal immunity.

van Spriel AB, Sofi M, Gartlan KH, van der Schaaf A, Verschueren I, Torensma R, Raymakers RA, Loveland BE, Netea MG, Adema GJ, Wright MD, Figdor CG. Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, University Medical Centre, Nijmegen, The Netherlands.

Immunoglobulin A (IgA) secretion by plasma cells in the immune system is critical for protecting the host from environmental and microbial infections. However, the molecular mechanisms underlying the generation of IgA(+) plasma cells remain poorly understood. Here, we report that the B cell-expressed tetraspanin CD37 inhibits IgA immune responses in vivo. CD37-deficient (CD37-/-) mice exhibit a 15-fold increased level of IgA in serum and significantly elevated numbers of IgA(+) plasma cells in spleen, mucosal-associated lymphoid tissue, as well as bone marrow. Analyses of bone marrow chimeric mice revealed that CD37-deficiency on B cells was directly responsible for the increased IgA production. We identified high local interleukin-6 (IL-6) production in germinal centers of CD37-/- mice after immunization. Notably, neutralizing IL-6 in vivo reversed the increased IgA response in CD37-/- mice. To demonstrate the importance of CD37-which can associate with the pattern-recognition receptor dectin-1-in immunity to infection, CD37-/- mice were exposed to Candida albicans. We report that CD37-/- mice are evidently better protected from infection than wild-type (WT) mice, which was accompanied by increased IL-6 levels and C. albicans-specific IgA antibodies. Importantly, adoptive transfer of CD37-/- serum mediated protection in WT mice and the underlying mechanism involved direct neutralization of fungal cells by IgA. Taken together, tetraspanin protein CD37 inhibits IgA responses and regulates the anti-fungal immune response.

PMID: 19282981 [PubMed - in process]