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APOBEC3 enzymes restrict marginal zone B cells.

ABSTRACT: In general, a long-lasting immune response to viruses is achieved when they are infectious and replication competent. In the mouse, the neutralizing antibody response to Friend murine leukemia virus is contributed by an allelic form of the enzyme Apobec3 (abbreviated A3). This is counterintuitive because A3 directly controls viremia before the onset of adaptive antiviral immune responses. It suggests that A3 also affects the antibody response directly. Here, we studied the relative size of cell populations of the adaptive immune system as a function of A3 activity. We created a transgenic mouse that expresses all seven human A3 enzymes and compared it to WT and mouse A3-deficient mice. A3 enzymes decreased the number of marginal zone B cells, but not the number of follicular B or T cells. When mouse A3 was knocked out, the retroelement hitchhiker-1 and sialyl transferases encoded by genes close to it were overexpressed three and two orders of magnitude, respectively. We suggest that A3 shifts the balance, from the fast antibody response mediated by marginal zone B cells with little affinity maturation, to a more sustained germinal center B-cell response, which drives affinity maturation and, thereby, a better neutralizing response.

SUBMITTER: Beck-Engeser GB

PROVIDER: S-EPMC4972502 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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APOBEC3 enzymes restrict marginal zone B cells.

Beck-Engeser Gabriele B GB Winkelmann Rebecca R Wheeler Matthew L ML Shansab Maryam M Yu Philipp P Wünsche Sarah S Walchhütter Anja A Metzner Mirjam M Vettermann Christian C Eilat Dan D DeFranco Anthony A Jäck Hans-Martin HM Wabl Matthias M

European journal of immunology 20150121 3

In general, a long-lasting immune response to viruses is achieved when they are infectious and replication competent. In the mouse, the neutralizing antibody response to Friend murine leukemia virus is contributed by an allelic form of the enzyme Apobec3 (abbreviated A3). This is counterintuitive because A3 directly controls viremia before the onset of adaptive antiviral immune responses. It suggests that A3 also affects the antibody response directly. Here, we studied the relative size of cell ...[more]

PMID: 25501566

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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.

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APOBEC3 enzymes restrict marginal zone B cells.

Publications

APOBEC3 enzymes restrict marginal zone B cells.

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