B cells from rheumatoid arthritis patients show important alterations on the expression of CD86 and FcgammaRIIb, which are modulated by anti-tumor necrosis factor therapy

Abstract

IntroductionSeveral molecules help preserve peripheral B cell tolerance, but when altered, they may predispose to autoimmunity. This work studied the expression of the costimulatory molecule CD86 and the inhibitory receptor for IgG immune complexes FcγRIIb (CD32b), on B cells from rheumatoid arthritis (RA) patients, and the influence of anti-tumor necrosis factor (TNF) therapy.MethodsPeripheral B cells from 18 RA patients and 13 healthy donors were characterized using flow cytometry. Eleven patients who underwent a six-month adalimumab therapy were further assessed for phenotypic changes on their B cells.ResultsRA patients exhibited a high percentage of naïve and memory B cells expressing CD86. In contrast, expression of FcγRIIb was significantly reduced on RA memory B cells and plasmablasts as compared to healthy donors, probably due to downregulation of this receptor when differentiating from naïve to memory cells. These alterations on FcγRIIb were associated with high levels of anti-citrullinated vimentin autoantibodies. In addition, treatment with adalimumab normalized the expression of CD86 on memory B cells and reduced the expression of FcγRIIb, mainly on naïve B cells.ConclusionsOur findings show that peripheral B cells from RA patients have an altered expression of key molecules, such as CD86 and FcγRIIb. Because this latter receptor is required for feedback inhibition, a deficient expression might contribute to humoral autoimmune responses. Furthermore, these molecules are likely to be influenced by inflammatory factors, since they were modulated by TNF inhibition.

CD40 Mediates Downregulation of CD32B on Specific Memory B Cell Populations in Rheumatoid Arthritis

“…Furthermore, we identify a subpopulation of CD32B low/neg cells in the CD27 + IgD 2 peripheral memory B cell subset, which is increased with age in both healthy individuals and in patients with RA. These data are consistent with previous reports, which showed that patients with active RA have reduced levels of CD32B expression on CD27 + memory B cells (14). Our findings demonstrate that this downregulation of CD32B on memory B cells is not present in all memory subsets; rather, it is primarily restricted to the CD27 with enhanced B cell activation and autoantibody production.…”

“…1 Expression of CD32B is reduced on CD27 + IgD -memory B cells in patients with active RA and is associated with high levels of autoantibody production CD32B expression on circulating B cells is downregulated in several autoimmune diseases. For example, CD27 positive memory B cells have decreased CD32B expression in patients with RA (14). Despite this knowledge, it is unclear whether this downregulation is restricted to specific memory B cell subsets or select populations within these subsets.…”

“…If steric hindrance were artificially inhibiting a-CD32B staining, we would expect that these three B cell subsets would exhibit changes in CD32B expression analogous to those observed in the CD27 + IgD 2 B subset in patients with high levels of autoantibodies. In addition to RA, the dysregulation of CD32B on B cells has been reported in several other autoimmune diseases (13)(14)(15). However, the mechanisms responsible for the B cell-specific downregulation of CD32B are uncertain.…”

“…Specifically, CD32B gene deficiency increases both the susceptibility to autoimmunity and disease severity in mice (9)(10)(11). In humans, decreased CD32B expression on B cells has been observed in patients with Ab-dependent autoimmune diseases, such as systemic lupus erythematosus (SLE), RA and chronic inflammatory demyelinating polyneuropathy (CIDP) (12)(13)(14)(15)(16). The precise population of B cells that are affected by CD32B downregulation is disease specific.…”

High frequencies of activated B cells and T follicular helper cells are correlated with disease activity in patients with new-onset rheumatoid arthritis

“…+ and CD95 + CD19 + B cells were significantly higher in the RA patients than that in the HC, consistent with a previous report [32,33]. These data indicated more activated B cells in RA patients.…”