IQGAP1 Promotes Early B Cell Development, is Essential for the Development of Marginal Zone (MZ) B Cells, and is Critical for Both T-dependent and T-independent Antibody Responses

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2024 Nov 25

PMID 39585462

Authors

Ravi K Lella

Subramaniam Malarkannan

Affiliations

Soon will be listed here.

Abstract

IQGAP1 is a multi-functional scaffold protein. However, its role in B cell development and function is unknown. Here, we show IQGAP1 as an essential scaffold that regulates early B cell development and function. Iqgap1 mice contained significantly increased numbers of B220 B, B220IgM pro/pre-B, and B220IgM immature-B cells in the bone marrow. In the spleens of the Iqgap1 mice, newly formed and follicular B cell numbers were increased, while the marginal zone B cell numbers were significantly reduced. Lack of IQGAP1 reduced T-dependent and T-independent humoral responses. Mechanistically, the lack of IQGAP1 considerably decreased the phosphorylation of Mek1/2, Erk1/2, and Jnk1/2. B cells from Iqgap1 mice failed to suppress IL-7R-mediated activation of Stat5a/b, an essential step for cell-cycle exit and initiate light-chain recombination, reducing RS rearrangement frequency. Our study provides the first evidence that IQGAP1-based signalosome is necessary for the development and functions of B cells.

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