Investigating the role of Apobec3 in immunoglobulin class switch recombination

Friday, November 08, 2013 — Poster Session IV
2:00 p.m. – 4:00 p.m.	FAES Academic Center (Upper-Level Terrace)	FDA/CBER	IMMUNO-2

Authors

A.P. Arudchandran
R.M. Bernstein
F.C. Mills
E.E. Max

Abstract

Mature B-cells undergo class switch recombination (CSR), a process causing IgM expressing cells to switch to IgG, IgE or IgA production. Switch recombination occurs between the μ switch region (S) and one of the downstream S regions of the heavy chain locus. Activation Induced Deaminase (AID) is known to trigger CSR by deaminating cytosines to uracils in the switch regions, thus facilitating DNA breaks. Even though AID knockout mice are unable to undergo robust class switch recombination, DNA breaks have been reported in the switch regions of these mice. Therefore, we searched for an alternate cytosine deaminase that could facilitate DNA breaks and lead to CSR. We identified Apobec3 as a likely candidate; we find that Apobec3 mRNA expression is up regulated, and that Apobec3 protein binds to the switch region of B-cells stimulated to undergo CSR (as shown by ChIP analysis). In addition, Apobec3 knockout mice revealed that Apobec3 contributes to single-strand DNA breaks of B cells undergoing CSR, and to the low level of IgG1 expression in AID knockout mice. Thus while Apobec3 is not necessary for CSR, it may make a small contribution to this process, as revealed in the absence of AID.