CD151 interacts with integrin beta 2 in B cell lymphomas.

in Cellular and molecular life sciences : CMLS by Philipp M Hagemann, Angelique N Kenyon, Alfredo Cabrera-Orefice, Abbey B Arp, Eva A M Hesius, Michiel van den Brand, Sjoerd J van Deventer, Daphne de Jong, Blanca Scheijen, Zijun Y Xu-Monette, Ulrich Brandt, Cornelia G Spruijt, Michiel Vermeulen, Martin Ter Beest, Ken H Young, Annemiek B van Spriel

TLDR

  • The study investigated CD151 expression in B cells and lymphomas, identifying a new interaction partner, ITGB2, and a potential target for immunotherapy in diffuse large B cell lymphoma.

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.

Overview

  • The study investigated CD151 expression in normal human B cells and B cell lymphomas using flow cytometry and immunohistochemistry.
  • CD151 expression increased during B cell differentiation, and B lymphoma cell lines and biopsy samples expressed higher levels compared to normal B cells.
  • The study aimed to investigate the function of CD151 in B cells and identified a new interaction partner, integrin beta 2 (ITGB2), and a potential target for immunotherapy.

Comparative Analysis & Findings

  • CD151 expression 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.
  • CD151-deficient lymphomas were identified, but CD151 expression was predominantly detected in the activated (ABC) subset of diffuse large B cell lymphoma (DLBCL).

Implications and Future Directions

  • The study identified a new molecular association of CD151 with ITGB2, and targeting integrin-free CD151 in DLBCL may represent a new target for immunotherapy.
  • Future studies can investigate the functional role of CD151 in B cells and its role in B cell malignancies.
  • The study highlights the need for further research to understand the expression and function of CD151 in B cell malignancies and its potential as a therapeutic target.
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