

Title | IgG3 regulates tissue-like memory B cells in HIV-infected individuals. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Kardava, 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 |
Journal | Nat Immunol |
Volume | 19 |
Issue | 9 |
Pagination | 1001-1012 |
Date Published | 2018 Sep |
ISSN | 1529-2916 |
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. |
DOI | 10.1038/s41590-018-0180-5 |
Alternate Journal | Nat. Immunol. |
PubMed ID | 30104633 |