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

Nat Immunol. 2018 Sep;19(9):1001-1012. doi: 10.1038/s41590-018-0180-5. Epub 2018 Aug 13.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • B-Lymphocytes / immunology*
  • C-Reactive Protein / metabolism
  • Cells, Cultured
  • Complement C1q / metabolism
  • Female
  • HIV Infections / immunology*
  • HIV-1 / physiology*
  • Humans
  • Immunoglobulin G / metabolism*
  • Immunoglobulin M / metabolism
  • Immunologic Memory
  • Immunomodulation
  • Male
  • Middle Aged
  • Protein Binding
  • Receptor Aggregation
  • Receptors, Antigen, B-Cell / metabolism*
  • Receptors, IgG / metabolism
  • Young Adult


  • Fc gamma receptor IIB
  • Immunoglobulin G
  • Immunoglobulin M
  • Receptors, Antigen, B-Cell
  • Receptors, IgG
  • Complement C1q
  • C-Reactive Protein