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

• Published in: Scientific reports Vol. 10; no. 1; p. 13156
• Main Authors: Azar, Ali A., Michie, Alison M., Tarafdar, Anuradha, Malik, Natasha, Menon, Geetha K., Till, Kathleen J., Vlatković, Nikolina, Slupsky, Joseph R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.08.2020; Nature Publishing Group
• Subjects: 631/250/1619/40; 631/67/1990/283/1895; 692/4028/67/1990/283/1895; Alternative splicing; Animals; Antigens, CD - genetics; Antigens, CD - metabolism; B-1 cells; B-cell receptor; B-Lymphocytes - enzymology; B-Lymphocytes - pathology; CD43 antigen; CD5 antigen; Chronic lymphocytic leukemia; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Leukemic; Humanities and Social Sciences; Immunoglobulin D; Immunoglobulin D - genetics; Immunoglobulin D - metabolism; Immunoglobulin M; Immunoglobulin M - genetics; Immunoglobulin M - metabolism; Kinases; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - enzymology; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - pathology; Lymphocytes B; Mammalian cells; Mice; Mice, Transgenic; multidisciplinary; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Peripheral blood; Peritoneum; Protein kinase; Protein kinase C; Protein Kinase C beta - biosynthesis; Protein Kinase C beta - genetics; Receptors, Antigen, B-Cell - genetics; Receptors, Antigen, B-Cell - metabolism; Science; Science (multidisciplinary); Signal Transduction; Spleen; Transgenic mice
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-70191-y

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 + IgM dim toward IgD dim IgM + 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 + IgM + CD43 neg CD21 + CD24 + ), increased populations of B-1 cells (B220 + IgD dim IgM + CD43 + CD24 + CD5 + ), and higher numbers of immature B cells (IgD dim IgM dim CD21 neg ) at the expense of mature B cells (IgD + IgM + CD21 + ). 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.