CD21^−/low B cells: A Snapshot of a Unique B Cell Subset in Health and Disease

Abstract

a These authors contributed equally. AbstractB cells represent one of the cellular components of the immune system that protects the individual from invading pathogens. In response to the invader, these cells differentiate into plasma cells and produce large amounts of antibodies that bind to and eliminate the pathogen. A hallmark of autoimmune diseases is the production of autoantibodies i.e. antibodies that recognize self. Those that are considered pathogenic can damage tissues and organs, either by direct binding or when deposited as immune complexes. For decades, B cells have been considered to play a major role in autoimmune diseases by antibody production. However, as pathogenic autoantibodies appear to derive mainly from T cell dependent responses, T cells have been the focus for many years. The successful treatment of patients with autoimmune diseases with either B cell depletion therapy (rituximab) or inhibition of B cell survival (belimumab), suggested that not only the autoantibodies but also other B cell features are important. This has caused a surge of interest in B cells and their biology resulting in the identification of various subsets e.g. regulatory B cells, several memory B cell subsets etc. Also, in other conditions such as chronic viral infections and primary immunodeficiency, several B cell subsets with unique characteristics have been identified. In this review, we will discuss one of these subsets, a subset that is expanded in conditions characterized by chronic immune stimulation. This B cell subset lacks, or expresses low, surface levels of the complement receptor 2 (CD21) and has therefore been termed CD21 À/low B cells.

B cells expressing the IgA receptor FcRL4 participate in the autoimmune response in patients with rheumatoid arthritis

“…Furthermore, a population of CD21 low/CD11c high B cells has been observed in peripheral blood of patients with a number of chronic diseases and in advanced age (reviewed by Thorarinsdottir et al. [43]). FcRL4+ cells were not detected in the majority of peripheral blood samples from RA patients, [14].…”

B‐cell responses to HIV infection

“…TLM B cells in HIV-viremic individuals also express FCRL4 and bear other similarities with tonsillar counterparts, including increased expression of CD20 and decreased response to B-cell stimuli (14). In HIV infection, as in other settings of chronic viremia with other pathogens or immune activation related to a variety of conditions (reviewed in (44, 47, 48)), several other inhibitory receptors are over-expressed on TLM or similar B cells, as well as the inflammatory chemokine receptor CXCR3 and adhesion molecule CD11c that have also been associated with LCMV-induced T-cell exhaustion (50). In this regard, HIV-associated B-cell exhaustion among TLM B cells has been described on the basis of cumulative properties and similarities with T-cell exhaustion (14).…”

Age‐associated B cells expanded in autoimmune mice are memory cells sharing H‐CDR3‐selected repertoires

“…Over the last decade, a distinct mature B‐cell population characterized by low levels/lack of CD21 (CD21 −/low ) has been described in both mice and humans . CD21, complement receptor 2, is otherwise expressed on mature B cells but not on early transitional B cells and plasma cells.…”