A novel transgenic mouse strain expressing PKC\u03b2II demonstrates expansion of B1 and marginal zone B cell populations

Ali A Azar,Kathleen J Till,Nikolina Vlatković,Geetha K Menon,Natasha Malik,Alison M Michie,Joseph R Slupsky,Anuradha Tarafdar

doi:10.1038/s41598-020-70191-y

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+IgMdim toward IgDdimIgM+ 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+CD43negCD21+CD24+), increased populations of B-1 cells (B220+IgDdimIgM+CD43+CD24+CD5+), and higher numbers of immature B cells (IgDdimIgMdimCD21neg) 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.

Highlights

B cell receptor (BCR) signaling plays an essential role at critical stages of B cell d evelopment[1,2]
We aimed to analyze the effect of PKCβII overexpression on the B cell compartment by generating a transgenic mouse strain where expression of PKCβII was driven by the Eμ promoter
Consistent with our initial hypothesis, the consequence of B cell-directed PKCβII overexpression is a proportional change in FO, marginal zone (MZ)-like, B-1 and immature B cell populations respectively in the spleen, peritoneum and peripheral blood of Eμ-PKCβIItg mice

Summary

Introduction

B cell receptor (BCR) signaling plays an essential role at critical stages of B cell d evelopment[1,2]. Key signaling molecules have been found to be intricately linked to the stage specific responses of BCR signaling While this is true for the early stages of B cell differentiation where this relationship is well defined, the roles of signaling molecules involved in B cell fate decisions in the periphery are less well characterized and u nderstood[2]. One such signaling molecule is Protein kinase Cβ (PKCβ), which plays a central role in the appropriate regulation of B cell development and activation, including BCR s ignaling[3]. Considering the role of PKCβ in modulating BCR signaling and in B cell development, the development of B-1 and MZ B cells, we hypothesized that transgenic expression of PKCβII within B cells of mice might lead to an expansion in populations of these B cell types

Objectives

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Conclusion