A double-edged sword in B-cell-targeted therapy for inflammatory diseases

Cells of the immune system, including B cells, perform inflammatory functions against microbial invasion, accompanied by anti-inflammatory responses to avoid host damage. B-cell-depletion therapy using anti-CD20 monoclonal antibodies against inflammatory diseases has beneficial or adverse effects depending on the timing and/or microenvironment in which they are used. To achieve effective B-cell-targeted therapy, it is necessary to identify and understand the modes of action of pathogenic and regulatory B cells, which include antibody production, formation of immune complexes, cytokine and chemokine production, cytotoxic killing, lymphoid neogenesis and antigen presentation. B cells interact with multiple cells, including dendritic cells, T cells and natural killer T cells, creating a complex regulatory network. Specific targeting of B-cell subsets and/or their interaction partners might lead to clinical benefits with minimal host damage.