Integrin β1 regulates marginal zone B cell differentiation and PI3K signaling

Abstract

Marginal zone (MZ) B cells represent innate-like B cells that mediate a fast immune response. The adhesion of MZ B cells to the marginal sinus of the spleen is governed by integrins. Here, we address the question of whether β1-integrin has additional functions by analyzing Itgb1fl/flCD21Cre mice in which the β1-integrin gene is deleted in mature B cells. We find that integrin β1–deficient mice have a defect in the differentiation of MZ B cells and plasma cells. We show that integrin β1–deficient transitional B cells, representing the precursors of MZ B cells, have enhanced B cell receptor (BCR) signaling, altered PI3K and Ras/ERK pathways, and an enhanced interaction of integrin-linked kinase (ILK) with the adaptor protein Grb2. Moreover, the MZ B cell defect of integrin β1–deficient mice could, at least in part, be restored by a pharmacological inhibition of the PI3K pathway. Thus, β1-integrin has an unexpected function in the differentiation and function of MZ B cells.

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