IgG3 regulates tissue-like memory B cells in HIV-infected individuals.

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TitleIgG3 regulates tissue-like memory B cells in HIV-infected individuals.
Publication TypeJournal Article
Year of Publication2018
AuthorsKardava, L, Sohn, H, Youn, C, Austin, JW, Wang, W, Buckner, CM, J Justement, S, Melson, VA, Roth, GE, Hand, MA, Gittens, KR, Kwan, RW, Sneller, MC, Li, Y, Chun, T-W, Sun, PD, Pierce, SK, Moir, S
JournalNat Immunol
Volume19
Issue9
Pagination1001-1012
Date Published2018 Sep
ISSN1529-2916
Abstract

Immunoglobulin G3 (IgG3) has an uncertain role in the response to infection with and vaccination against human immunodeficiency virus (HIV). Here we describe a regulatory role for IgG3 in dampening the immune system-activating effects of chronic HIV viremia on B cells. Secreted IgG3 was bound to IgM-expressing B cells in vivo in HIV-infected chronically viremic individuals but not in early-viremic or aviremic individuals. Tissue-like memory (TLM) B cells, a population expanded by persistent HIV viremia, bound large amounts of IgG3. IgG3 induced clustering of B cell antigen receptors (BCRs) on the IgM B cells, which was mediated by direct interactions between soluble IgG3 and membrane IgM of the BCR (IgM-BCR). The inhibitory IgG receptor CD32b (FcγRIIb), complement component C1q and inflammatory biomarker CRP contributed to the binding of secreted IgG3 onto IgM-expressing B cells of HIV-infected individuals. Notably, IgG3-bound TLM B cells were refractory to IgM-BCR stimulation, thus demonstrating that IgG3 can regulate B cells during chronic activation of the immune system.

DOI10.1038/s41590-018-0180-5
Alternate JournalNat. Immunol.
PubMed ID30104633