title: 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.
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, CA, USA.
authors.forename: Gabriele B
authors.initials: GB
authors.lastname: Beck-Engeser
authors.forename: Rebecca
authors.initials: R
authors.lastname: Winkelmann
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Wheeler
authors.forename: Maryam
authors.initials: M
authors.lastname: Shansab
authors.forename: Philipp
authors.initials: P
authors.lastname: Yu
authors.forename: Sarah
authors.initials: S
authors.lastname: Wünsche
authors.forename: Anja
authors.initials: A
authors.lastname: Walchhütter
authors.forename: Mirjam
authors.initials: M
authors.lastname: Metzner
authors.forename: Christian
authors.initials: C
authors.lastname: Vettermann
authors.forename: Dan
authors.initials: D
authors.lastname: Eilat
authors.forename: Anthony
authors.initials: A
authors.lastname: DeFranco
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Jäck
authors.forename: Matthias
authors.initials: M
authors.lastname: Wabl
mesh_terms: D000071478:APOBEC Deaminases; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D003564:Cytidine Deaminase / Q000235:genetics / Q000276:immunology*; D043525:Cytosine Deaminase / Q000235:genetics / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology
chemical_list: D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; C503504:Apobec3 protein, mouse; D003564:Cytidine Deaminase
keywords: Apobec3; B cell; Hitchhiker-1; Recovery from Friend virus 3 (Rfv3); Sialyl transferases