BAFF augments IgA2 and IL‐10 production by TLR7/8 stimulated total peripheral blood B cells

Abstract

Class‐switching of B cells to IgA can be induced via both T‐cell‐dependent and T‐cell‐independent mechanisms. IgA is most predominantly produced mucosally and is important for combating infections and allergies. In contrast to mice, humans have two forms of IgA; IgA1 and IgA2 with diverse tissue distribution. In early life, IgA levels might be sub‐optimal especially during the fall season when bacterial and viral infections are more common. Therefore, we investigated using human B cells whether T‐cell‐independent factors ‐promoting cell survival, class switching and immunoglobulin secretion‐ BAFF, APRIL, IL‐10 and retinoic acid can boost IgA production in the context of viral or bacterial infection. To this end total and naive peripheral blood B cells were stimulated with these factors for 6 days in the presence or absence of TLR7/8 agonist R848 (mimicking viral infection) or TLR9 agonist CpG‐ODN (mimicking bacterial infection). We show that BAFF significantly augments IgA2 production in TLR7/8 stimulated mature, but not naïve B cells. In addition, BAFF augments IL‐10 production and viability in TLR7/8 and TLR9 stimulated mature B cells. These data warrant further investigation of its role in immune regulation both in the periphery and mucosal tissues in early life or during disease.

9‐cis Retinoic acid and 1.25‐dihydroxyvitamin D3 drive differentiation into IgA+ secreting plasmablasts in human naïve B cells

“…The comparison between T‐cell independent activation of human B cell subsets with Staphylococcus aureus and CpG revealed that 9cRA exerts both inhibiting and promoting effects on cell differentiation [35,36]. Noteworthy, both, naïve and mature human B cells stimulated with TLR7/8 or TLR9 significantly upregulated CD38 in the presence of RA [11]. That RA signaling is essential for B cell maturation has also been demonstrated in a mouse model with silenced RA signaling in the B cell lineage resulting in developmental defects of MZ and B1 B cells [37].…”

“…Moreover, 9cRA can modulate the allergic immune response by promoting an IgA response [4]. In addition, RA augments IgA 1 and IgA 2 production in TLR7/8 or TLR9 stimulated mature B cells [11].…”

Analysis of the dysregulation between regulatory B and T cells (Breg and Treg) in human immunodeficiency virus (HIV)-infected patients

“…In this context, it was already observed that some factors such as B Cell-Activating Factor (BAFF), responsible for the B-cell maturation and survival, were elevated and associated with progressive diseases in HIV + individuals [47, 48]. BAFF is as well a factor that was related to a high level of IL-10 [48], IL-10-producing B-cell frequency [49, 50] and Treg differentiation in mice models [51]. Therefore, IL-10-producing B cells and expansion of Treg have been related to the expression of BAFF.…”

Altered circulating T follicular helper cells in patients with chronic immune thrombocytopenia

“…Notably, IL-10 is abundantly produced in healthy persons ( 14 ). Xin et al ( 15 ) identified that IL-10-producing TFH cells have an increased capacity to form stable TFH-B cell conjugates compared with their IL-10-TFH counterparts, suggesting that IL-10 + TFH cells may specialize in providing distress signals to B cells during chronic infection.…”