Marginal zone B cells: From housekeeping function to autoimmunity?

J Autoimmun. 2021 May;119:102627. doi: 10.1016/j.jaut.2021.102627. Epub 2021 Feb 25.


Marginal zone (MZ) B cells comprise a subset of innate-like B cells found predominantly in the spleen, but also in lymph nodes and blood. Their principal functions are participation in quick responses to blood-borne pathogens and secretion of natural antibodies. The latter is important for housekeeping functions such as clearance of apoptotic cell debris. MZ B cells have B cell receptors with low poly-/self-reactivity, but they are not pathogenic at steady state. However, if simultaneously stimulated with self-antigen and pathogen- and/or damage-associated molecular patterns (PAMPs/DAMPs), MZ B cells may participate in the initial steps towards breakage of immunological tolerance. This review summarizes what is known about the role of MZ B cells in autoimmunity, both in mouse models and human disease. We cover factors important for shaping the MZ B cell compartment, how the functional properties of MZ B cells may contribute to breaking tolerance, and how MZ B cells are being regulated.

Keywords: Autoimmunity; Lymph nodes; Marginal zone B cell; Spleen.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation
  • Autoantibodies / immunology
  • Autoantigens / immunology
  • Autoimmunity*
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism*
  • Biomarkers
  • Disease Susceptibility
  • Homeostasis / immunology*
  • Humans
  • Immunomodulation
  • Immunophenotyping
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Organ Specificity
  • Receptors, Antigen, B-Cell / metabolism
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism


  • Autoantibodies
  • Autoantigens
  • Biomarkers
  • Receptors, Antigen, B-Cell