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

Scand J Immunol. 2015 Sep;82(3):254-61. doi: 10.1111/sji.12339.


B 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(-/low) B cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use
  • Autoantibodies / immunology
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / immunology*
  • B-Lymphocyte Subsets / immunology*
  • HIV Infections / immunology
  • HIV Infections / virology
  • Humans
  • Immunologic Memory / immunology
  • Immunosuppressive Agents / therapeutic use*
  • Lymphocyte Depletion
  • Receptors, Complement 3d / genetics*
  • Receptors, Complement 3d / immunology
  • Rituximab


  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Autoantibodies
  • Immunosuppressive Agents
  • Receptors, Complement 3d
  • Rituximab
  • belimumab