T-cell regulation of IgG subclass expression by mitogen-induced plasma cells: Soluble factors versus the T cells

Abstract

The human IgG subclasses expressed by plasma cells generated from circulating B cells in response to soluble T-cell factors were examined by immunofluorescence using subclass-specific monoclonal antibodies. Soluble T-cell factors were induced by a mixed lymphocyte reaction, pokeweed mitogen (PWM), or phytohemagglutinin. The distribution of IgG subclasses expressed by plasma cells induced by these factors was IgG2 greater than 75%, IgG1 less than 25%, IgG3 less than 1%, and IgG4 less than 1%. On the other hand, IgG1 was dominant when B cells were cultured with T cells and PWM: IgG1 approximately 70%, IgG2 approximately 20%, IgG3 approximately 8%, and IgG4 approximately 1%. The addition of different amounts of the T-cell factors to B cells in culture did not alter the predominance of IgG2 plasma-cell differentiation. These results suggest that T cells and their soluble factors may preferentially enhance terminal differentiation of different IgG B-cell subpopulations. In contrast, the ratio of IgA1 to IgA2 plasma-cell responses was approximately 1.5 to 1 regardless of whether the B-cell precursors were induced by T-cell factors or by the T cells plus PWM.

Evolution of ADAMTS13 antibodies in a fatal case of thrombotic thrombocytopenic purpura

“…However, IgG 2 may dominate the immune responses to carbohydrates or microorganisms such as Actinobacillus actinomycetemcomitans in patients with periodontitis9. IgG 2 responses may be driven by platelet derived growth factor; prostaglandin E 2; Th1-type cytokines such as interferon-γ (IFN-γ), TGF-β, IL-2, and IL-6; and perhaps other unknown T-cell or monocyte-derived factors10–14. Actinobacilli may induce predominant IgG 2 response by acting on dendritic cells to produce IL-12, which in turn induces natural killer cells to produce IFN-γ15.…”

IgG and IgM cooperate in coating of intestinal bacteria in IgA deficiency

“…However, we find a 1.6-fold increased prevalence of IgA− vs. IgA+ subjects with single-IgG2 bacterial coating. Factors promoting isotype switching to IgG2 are largely unexplored 33 , but it is reported that IgG2 may be induced by the type 1 immune cytokines IFN-ɣ, IL-12 and IL-18 34 , 35 , by specific pathogenic microbes 35 , 36 , and in response to E. coli -derived LPS stimulation in vitro 37 , thereby supporting a link between the presence of hexa-acylated LPS-producing bacteria, such as E. coli , and IgG2 production. Enhanced systemic TNF-α levels in subjects with single-IgG2 coated bacteria, and increased prevalence in Crohn’s disease patients with active disease, further substantiate that single-IgG2 coating is linked to local and systemic inflammation, and may be a marker for on-going inflammatory processes.…”