Antigen-presenting human B cells are expanded in inflammatory conditions

Abstract

Traditionally, B cells have been best known for their role as producers of antibodies. However, in recent years, a growing body of evidence has accumulated showing that B cells fulfill a range of other immunologic functions. One of the functions that has attracted increasing attention is the capacity of B cells to induce antigen-specific activation of T cells through presentation of antigens. However, the analysis of this B cell function has been hampered by the lack of a phenotypically well-defined antigen-presenting B cell subset. Here, we report the identification of a human antigen-presenting B cell subset with strong immunostimulatory properties. This B cell subset is characterized by low expression of CD21 and high expression of the activation marker CD86 and exhibits strong T cell-stimulatory activity, as demonstrated by means of an autologous mixed-lymphocyte reaction. Phenotypically, CD21CD86 immunostimulatory B cells (B) represented CD27 class-switched IgMIgD B lymphocytes and displayed a higher expression of cell surface receptors, which mediate the migration from peripheral blood to sites of inflammation. Flow cytometric analysis of peripheral blood obtained from individuals with inflammatory conditions revealed that the B subset was expanded following vaccination and in patients with rheumatoid arthritis. Taken together, our work shows that B represents a strongly immunostimulatory B cell subset, which could be a promising target for immunotherapeutic intervention in inflammatory diseases.

Tumor-associated B cells and humoral immune response in head and neck squamous cell carcinoma

“…Gating of these populations was adopted from previous publications investigating the respective subsets. 13,24 There was no significant difference in percentages of B cells in the CD45 + compartment of PBMC HC, PBMC HNSCC, HNSCC tumor tissue and mucosa samples ( Figure 1B). HPV + HNSCC demonstrated increased percentages of tumor-infiltrating CD45 + lymphocytes (5.68 ± 4.32%) compared to HPV − tumors (2.26 ± 2.99%; p = 0.044) and non-cancerous mucosa (1.80 ± 3.59%; p = 0.039; Figure 1C).…”

“…Additionally, B cells serve as antigen-presenting cells and have the capacity to activate T cells. 13 Tertiary lymphoid structures (TLS) in the TME have been linked to this orchestrated B-T cell interaction and their presence to improved patient survival in multiple cancer entities including oral squamous cell carcinoma (OSCC). 14,15 By secretion of various cytokines, B cells can also shape the immune response in the TME in a pro-or antitumor direction.…”

Human monocytic myeloid‐derived suppressor cells impair B‐cell phenotype and function in vitro

“…The significant reduction of HLA-DR + , CD80 + , and CD86 + B-cell subsets is of high interest, as these molecules are essentially involved in B cell-driven antigen-presentation ( Fig. 5B-D) [41]. These results allow us to speculate that M-MDSCs may be able to interfere with the B-cell inherent capacity to present antigen to their cognate T cell.…”

B cell‐specific protein FCRLA is expressed by plasmacytoid dendritic cells in humans

“…pDCs and B cells are both professional antigen presenting cells (although not as potent as mDCs): they express MHC class II molecules, Toll-like receptors TLR7 and TLR9, and are able to present antigens to CD41 T cells (18,19). These FCRLApositive pDCs had lin-CD11c-CD1231 CD3031 HLA-DR1 phenotype and constitute 6-24% of the total pDC population in blood of healthy donors.…”

“…Being different cell types, pDCs and B cells, however, share some common features. pDCs and B cells are both professional antigen presenting cells (although not as potent as mDCs): they express MHC class II molecules, Toll-like receptors TLR7 and TLR9, and are able to present antigens to CD41 T cells (18,19). pDCs and B cells also possess a similar ability to reorganize their ERmachinery and to produce large amounts of secreted proteins in response to appropriate stimuli, pDCs produce type I IFNs and B cells produce immunoglobulins.…”