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

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⁺IgM^dim toward IgD^dimIgM⁺ 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^negCD21⁺CD24⁺), increased populations of B-1 cells (B220⁺IgD^dimIgM⁺CD43⁺CD24⁺CD5⁺), and higher numbers of immature B cells (IgD^dimIgM^dimCD21^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.

SUBMITTER: Azar AA

PROVIDER: S-EPMC7403146 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Azar Ali A AA Michie Alison M AM Tarafdar Anuradha A Malik Natasha N Menon Geetha K GK Till Kathleen J KJ Vlatković Nikolina N Slupsky Joseph R JR

Scientific reports 20200804 1

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< ...[more]

PMID: 32753714

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Project description:In 2016 there were an estimated 7,460 newly diagnosed patients with marginal zone lymphoma (MZL) in the US, which comprised 7% of all mature non-Hodgkin lymphomas (NHL). Based on data from the US SEER-18 program from 2001-2017, the age-standardized incidence rate for MZL was 19.6 per 1,000,000 person-years; 9% of MZL cases were splenic MZL (SMZL), 30% nodal MZL (NMZL), and 61% extranodal MZL (EMZL) of mucusa-associated lymphoid tissue (MALT). Incidence rates were slightly higher in men for SMZL and NMZL, but similar for EMZL, and increased steeply with age for all MZL subtypes. The incidence (age-standardized per 1,000,000) of MZL was highest among non-Hispanic whites (20.7), followed by Hispanics of all races (17.6), non-Hispanic blacks (15.4), and Asian/Pacific islanders (15.0). The incidence of MZL increased +1.0% per year in the US from 2001-2017, with increases reported in other countries during this timeframe. The 5-year relative survival rate for MZL in the US was 89.8% and was similar across racial/ethnic groups and by sex; survival rates have been increasing in the US and other countries. Established risk factors for MZL (or MZL subtypes) include family history of NHL, genetic loci in the HLA region, Helicobacter pylori infection (gastric MALT lymphoma), and several autoimmune diseases (Sjögren syndrome, systemic lupus erythematosus and Hashimoto thyroiditis), with strong (but not definitive) evidence for Chlamydia psittaci (ocular adnexal MALT lymphoma), Borrelia burgdorferi (cutaneous MZL), hepatitis C virus, human immunodeficiency virus, and solid organ transplantation. Promising risk factors that require additional study include other infections, other autoimmune conditions, trichloroethylene exposure, certain occupations, hair dye, cigarette smoking, sun exposure (protective), and alcohol use (protective). MZL is a model of an antigen-driven malignancy, where epidemiologic risk factors, tissue-specific factors, and host immune response (including the impact of chronic inflammation and immunosuppression) drive lymphomagenesis with implications for prevention.

Dataset Information

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

Publications

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

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