A novel transgenic mouse strain expressing PKCβII demonstrates expansion of B1 and marginal zone B cell populations



Azar, Ali A, Michie, Alison M, Tarafdar, Anuradha, Malik, Natasha, Menon, Geetha K, Till, Kathleen J ORCID: 0000-0002-3172-5771, Vlatkovic, Nikolina ORCID: 0000-0003-3003-794X and Slupsky, Joseph R ORCID: 0000-0002-7410-9004
(2020) A novel transgenic mouse strain expressing PKCβII demonstrates expansion of B1 and marginal zone B cell populations. SCIENTIFIC REPORTS, 10 (1). 13156-.

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Abstract

Protein kinase Cβ (PKCβ) expressed in mammalian cells as two splice variants, PKCβI and PKCβII, functions in the B cell receptor (BCR) signaling pathway and contributes to B cell development. We investigated the relative role of PKCβII in B cells by generating transgenic mice where expression of the transgene is directed to these cells using the Eµ promoter (Eµ-PKCβIItg). Our findings demonstrate that homozygous Eµ-PKCβIItg mice displayed a shift from IgD<sup>+</sup>IgM<sup>dim</sup> toward IgD<sup>dim</sup>IgM<sup>+</sup> B cell populations in spleen, peritoneum and peripheral blood. Closer examination of these tissues revealed respective expansion of marginal zone (MZ)-like B cells (IgD<sup>+</sup>IgM<sup>+</sup>CD43<sup>neg</sup>CD21<sup>+</sup>CD24<sup>+</sup>), increased populations of B-1 cells (B220<sup>+</sup>IgD<sup>dim</sup>IgM<sup>+</sup>CD43<sup>+</sup>CD24<sup>+</sup>CD5<sup>+</sup>), and higher numbers of immature B cells (IgD<sup>dim</sup>IgM<sup>dim</sup>CD21<sup>neg</sup>) at the expense of mature B cells (IgD<sup>+</sup>IgM<sup>+</sup>CD21<sup>+</sup>). Therefore, the overexpression of PKCβII, which is a phenotypic feature of chronic lymphocytic leukaemia cells, can skew B cell development in mice, most likely as a result of a regulatory influence on BCR signaling.

Item Type: Article
Uncontrolled Keywords: B-Lymphocytes, Animals, Mice, Transgenic, Mice, Immunoglobulin D, Immunoglobulin M, Receptors, Antigen, B-Cell, Neoplasm Proteins, Antigens, CD, Signal Transduction, Gene Expression Regulation, Enzymologic, Gene Expression Regulation, Leukemic, Leukemia, Lymphocytic, Chronic, B-Cell, Protein Kinase C beta
Depositing User: Symplectic Admin
Date Deposited: 29 Jul 2020 13:16
Last Modified: 14 Oct 2023 11:46
DOI: 10.1038/s41598-020-70191-y
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3095571