Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease of immune dysregulation affecting the joints. While T cells play recognised role in pathogenesis, presence autoantibodies years before clinical onset disease, and efficacy B cell-depleting therapy rituximab, highlight pathogenic for these functionally diverse lymphocytes. A novel subset, termed age-associated (ABCs), are de...

B-cell responses are guided by the integration of signals through the B-cell receptor (BCR), CD40, and cytokine receptors. The common γ chain (γc)-binding cytokine interleukin (IL)-21 drives humoral immune responses via STAT3-dependent induction of transcription factors required for plasma cell generation. We investigated additional mechanisms by which IL-21/STAT3 signaling modulates human B-ce...

4 cell receptor (BCR) triggering and T cell help induced initial B cell proliferation but were not sufficient to sustain prolonged survival and accumulation of B cells. Extensive proliferation, isotypic switch and differentiation to Ig-secreting cells were promoted by microbial agents acting on TLRs expressed by naïve B cells upon BCR stimulation. This finding demonstrates that humoral immune r...

Unseparated peripheral blood mononuclear cells (PBMCs) obtained from drug-naïve African individuals living in a context of multi-infections and presenting with high viral load (VL), were cultured in vitro and tested for their ability to produce antibodies (Abs) reacting with HIV-1 antigens. Within these PBMCs, circulating B cells were differentiated in vitro and produced IgG Abs against not onl...

Background: 17β-estradiol (E2) has been known to modulate immune response. Recent studies indicate that E2 at pregnancy level plays a role in regulating T cell response. Objective: To investigate the optimum dose of E2 (from 10-9 to 10-7 M) in mediating the generation of regulatory T cells (Tregs), using naïve human CD4+ T cells from healthy women. Methods: Naïve peripheral T cells were purifie...

Expression of selected genes in hematopoietic stem cells has been identified as a regulator of differentiation of B cells in the liver and bone marrow. Moreover, naïve B cells expressing surface immunoglobulin need other types of genes for antigen-dependent development in secondary lymphoid organs. Many advanced molecular mechanisms underlying primary antibody deficiencies in humans have been d...

HIV infection is associated with high rates of osteopenia and osteoporosis, but the mechanisms involved are unclear. We recently reported that bone loss in the HIV transgenic rat model was associated with upregulation of B cell expression of the key osteoclastogenic cytokine receptor-activator of NF-κB ligand (RANKL), compounded by a simultaneous decline in expression of its physiological moder...

Signals derived from the BCR (B-cell antigen receptor) control survival, development and antigenic responses. One mechanism by which BCR signals may mediate these responses is by regulating cell metabolism. Indeed, the bioenergetic demands of naïve B-cells increase following BCR engagement and are characterized by a metabolic switch to aerobic glycolysis; however, the signalling pathways involv...