Transforming growth factor beta 1 selectivity stimulates immunoglobulin G2b secretion by lipopolysaccharide-activated murine B cells.

Abstract

Bacterial lipopolysaccharide (LPS) has been reported to induce immunoglobulin (Ig)G2b class switching, yet we observed strain differences in IgG2b secretion in response to this mitogen. Specifically, BALB/c B cells, unlike those from DBA/2, synthesized relatively low amounts of IgG2b relative to IgG3, IgG1, or IgM. This report demonstrates that transforming growth factor (TGF) beta 1, previously shown to induce IgA class switching, selectively stimulates IgG2b secretion by BALB/c resting B cells activated with LPS. This activity was specifically reversed with a neutralizing anti-TGF-beta 1 antibody. The ability of TGF-beta 1 to act directly on highly purified membrane (m)IgM+ mIgG2b- cells to stimulate IgG2b production, stimulate an increase in IgG2b-secreting cells, and selectively increase the steady-state levels of germline gamma 2b RNA, suggests that it promotes IgG2b class switching. In this regard, addition of anti-TGF-beta antibody to cultures of DBA/2-derived resting B cells activated by LPS, alone, led to selective reduction in IgG2b secretion, indicating that endogenous TGF-beta 1 accounts for the high IgG2b secretory response observed in that strain. Finally, TGF-beta 1 failed to stimulate IgG2b secretion by B cells activated with dextran-conjugated anti-IgD antibody. We propose that TGF-beta 1 is a switch factor for the murine IgG2b subclass for appropriately activated B cells. In combination with other data, this would show that all six non-IgM, non-IgD isotypes in the mouse can be selectively induced by specific cytokines.

Synovial Fluid Cytokines in Patients with Rheumatoid Arthritus or Other Arthritic Lesions

“…No other cytokine was correlated with IgG2bIF. As IgG2bIF is not yet fully characterized, there have been suggestions that it might be identical to other cytokines, such as TGF-b [24]. However, here we show that IgG2bIF is not closely correlated with any other cytokine in the SF samples, which rules out identity with any of the cytokines included in this study.…”

“…TGF-b may be important in cartilage repair, as it can induce collagen synthesis [39]. At lower concentrations, TGF-b is a switch factor for immunoglobulin A (IgA) production [40][41][42] and it is necessary for production of all IgG subclasses in murine B cells [43] and for the induction of IgG2b production [24,31]. As high RF titres are a characteristic feature of RA, a potential pathogenic role for TGF-b might be to locally stimulate antibody production.…”

TGF-β1 Stimulates Mouse Macrophages to Express APRIL through Smad and p38MAPK/CREB Pathways

“…Ig isotype switching is a critical event in B-cell differentiation, and TGF-β1 is a specific switching factor for the IgA and IgG2b mouse isotype (Kim and Kagnoff, 1990;McIntyre et al, 1993). Since we have previously demonstrated that TGF-β1 stimulates mouse macrophages to express BAFF (Kim et al, 2008), it was worthwhile to investigate if TGF-β1 can modulate macrophages to express another member of the same family, APRIL.…”

IFN-γ Secreted by CD103+ Dendritic Cells Leads to IgG Generation in the Mesenteric Lymph Node in the Absence of Vitamin A

“…Purified naive B cells were activated with 10 mg/ml anti-mouse IgM F(ab9) 2 Ab with DCs from MLN of control or VAD mice. Recombinant mouse IL-5 (10 ng/ml; R&D Systems, Minneapolis, MN), ATRA (100 nM; Sigma-Aldrich), and RA antagonist LE540 (100 nM; Wako, Japan) were used in an in vitro culture system.…”