CD151 interacts with integrin beta 2 in B cell lymphomas.

Abstract

CD151 is a broadly expressed four-transmembrane protein (tetraspanin) that interacts with laminin-binding integrins like integrin alpha 3 (ITGA3). CD151 drives tumor development and expression correlates with poor prognosis in solid cancers, but CD151 has not been studied in B cell malignancies. We investigated CD151 expression on normal human B cells and B cell lymphomas using highly sensitive flow cytometry and immunohistochemistry. Expression of CD151 increased during B cell differentiation from naïve to memory B cells to plasma cells. B lymphoma cell lines and human lymphoma biopsy samples expressed higher levels of CD151 compared to normal B cells, but CD151-deficient lymphomas were identified as well. To investigate the function of CD151 in B cells, CD151-deficient and stably transduced CD151 expressing B lymphoma cell lines were generated. Immunoprecipitation-mass spectrometry analysis of CD151 protein complexes identified integrin beta 2 (ITGB2) as new interaction partner in lymphoma cells. Deficiency of CD151 decreased cell surface expression of alpha integrin subunits L (ITGAL) and M (ITGAM), and impaired ICAM-1-mediated cell spreading. Interestingly, B cells and lymphomas did not express ITGA3-bound CD151 compared to T cells that expressed two different populations of integrin-bound and integrin-free CD151. Despite CD151 expression not being related to clinical outcome of patients with diffuse large B cell lymphoma (DLBCL), CD151 expression was predominantly detected in the activated (ABC) subset of DLBCL. Taken together, we identified a new molecular association of CD151 with ITGB2, and targeting integrin-free CD151 in DLBCL may represent a new target for immunotherapy.