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

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...

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Veröffentlicht in:Scientific reports 2020-08, Vol.10 (1), p.13156-13156, Article 13156
Hauptverfasser: Azar, Ali A., Michie, Alison M., Tarafdar, Anuradha, Malik, Natasha, Menon, Geetha K., Till, Kathleen J., Vlatković, Nikolina, Slupsky, Joseph R.
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Sprache:eng
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Zusammenfassung: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-70191-y