Regulation of B‐cell function and expression of CD11c, T‐bet, and FcRL5 in response to different activation signals

• Published in: European journal of immunology 2024-08, Vol.54 (8), p.e2350736-n/a
• Main Authors: Kleberg, Linn, Courey‐Ghaouzi, Alan‐Dine, Lautenbach, Maximilian Julius, Färnert, Anna, Sundling, Christopher
• Format: Article
• Language: English
• Subjects: Animals; Atypical B cells; B cells; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; CD11c; CD11c antigen; CD11c Antigen - metabolism; Cell activation; Cell culture; Cell differentiation; Cell Differentiation - immunology; Cells, Cultured; Double‐negative B cells; FcRL5; Gene Expression Regulation - immunology; Humans; Interferon-gamma - immunology; Interferon-gamma - metabolism; Interleukin-6 - metabolism; Lymphocyte Activation - immunology; Lymphocytes B; Malaria; Medicin och hälsovetenskap; Mice; Receptors, Antigen, B-Cell - immunology; Receptors, Antigen, B-Cell - metabolism; Receptors, Fc - immunology; Receptors, Fc - metabolism; Signal Transduction - immunology; T-Box Domain Proteins - genetics; T-Box Domain Proteins - metabolism; TLR9 protein; Toll-Like Receptor 9 - immunology; Toll-Like Receptor 9 - metabolism; Toll-like receptors; T‐bet
• ISSN: 0014-2980; 1521-4141; 1521-4141
• DOI: 10.1002/eji.202350736

CD11c, FcRL5, or T‐bet are commonly expressed by B cells expanding during inflammation, where they can make up >30% of mature B cells. However, the association between the proteins and differentiation and function in the host response remains largely unclear. We have assessed the co‐expression of CD11c, T‐bet, and FcRL5 in an in vitro B‐cell culture system to determine how stimulation via the BCR, toll‐like receptor 9 (TLR9), and different cytokines influence CD11c, T‐bet, and FcRL5 expression. We observed different expression dynamics for all markers, but a largely overlapping regulation of CD11c and FcRL5 in response to BCR and TLR9 activation, while T‐bet was strongly dependent on IFN‐γ signaling. Investigating plasma cell differentiation and APC functions, there was no association between marker expression and antibody secretion or T‐cell help. Rather the functions were associated with TLR9‐signalling and B‐cell‐derived IL‐6 production, respectively. These results suggest that the expression of CD11c, FcRL5, and T‐bet and plasma cell differentiation and improved APC functions occur in parallel and are regulated by similar activation signals, but they are not interdependent. B cells stimulated with anti‐Ig (B‐cell receptor), CpG‐C (TLR9), and IFN‐g upregulate CD19, CD11c, T‐bet, and FcRL5, produce IL6 and IL10, support CD4+ T‐cell division and differentiate to plasma cells. CpG‐C drives CD19 upregulation, IL10‐production and plasma cell differentiation, but not T‐cell help. IFN‐g drives optimal T‐bet expression, but not cytokine secretion or plasma cell formation.