PreprintArticleVersion 1Preserved in Portico This version is not peer-reviewed
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
Version 1
: Received: 6 July 2023 / Approved: 6 July 2023 / Online: 7 July 2023 (08:50:00 CEST)
How to cite:
Lella, R.K.; Malarkannan, S. 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. Preprints2023, 2023070442. https://doi.org/10.20944/preprints202307.0442.v1
Lella, R.K.; Malarkannan, S. 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. Preprints 2023, 2023070442. https://doi.org/10.20944/preprints202307.0442.v1
Lella, R.K.; Malarkannan, S. 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. Preprints2023, 2023070442. https://doi.org/10.20944/preprints202307.0442.v1
APA Style
Lella, R.K., & Malarkannan, S. (2023). 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. Preprints. https://doi.org/10.20944/preprints202307.0442.v1
Chicago/Turabian Style
Lella, R.K. and Subramaniam Malarkannan. 2023 "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" Preprints. https://doi.org/10.20944/preprints202307.0442.v1
Abstract
IQGAP1 is a multi-functional scaffold protein. However, its role in B cell development and function is not known. Here, we demonstrate Iqgap1mice contained significantly increased numbers of B220+ B, B220+IgM pro/pre-B, and B220+IgM+ immature-B cells in the bone marrow. Here, we show IQGAP1 as the essential scaffold that regulates early B cell development and function. Iqgap1mice contained significantly increased numbers of B220+ B, B220+IgM pro/pre-B, and B220+IgM+ immature-B cells in the bone marrow. New-forming and follicular B cell numbers were increased, while the marginal zone B cell numbers were significantly reduced in the spleen of the Iqgap1mice. 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 Iqgap1mice failed to suppress IL-7R-mediated activation of Stat5a/b, an essential step for cell-cycle exit and initiate light-chain recombination, leading to a reduction in RS rearrangement frequency. Lack of IQGAP1 resulted in a significant reduction of IRF4 and IRF8 in BM B cells. Our study provides the first evidence that IQGAP1-based signalosome is essential for the development and functions of B cells.
Keywords
IQGAP1; B cell; MAPK; IQGAP1 signalosome
Subject
Biology and Life Sciences, Immunology and Microbiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
