Hypergammaglobulinemia and autoantibody induction mechanisms in viral infections

Nat Immunol. 2003 Apr;4(4):343-9. doi: 10.1038/ni911. Epub 2003 Mar 10.


Polyclonal hypergammaglobulinemia is a characteristic of chronic inflammatory conditions, including persisting viral infections and autoimmune diseases. Here we have studied hypergammaglobulinemia in mice infected with lymphocytic choriomeningitis virus (LCMV), which induces nonspecific immunoglobulins as a result of switching natural IgM specificities to IgG. The process is dependent on help from CD4+ T cells that specifically recognize LCMV peptides presented by B cells on major histocompatibility complex class II molecules. Thus, hypergammaglobulinemia may arise when specific helper T cells recognize B cells that have processed viral antigens irrespective of the B cell receptor specificity. This nonspecific B cell activation may contribute to antibody-mediated autoimmunity.

MeSH terms

  • Animals
  • Antigens, Viral / immunology
  • Arenaviridae Infections / complications
  • Arenaviridae Infections / immunology*
  • Autoantibodies / biosynthesis
  • Autoantibodies / immunology
  • Autoimmunity / immunology*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / virology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • Cytokines / metabolism
  • Hypergammaglobulinemia / etiology
  • Hypergammaglobulinemia / immunology*
  • Lymphocytic choriomeningitis virus / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Cell Surface / metabolism
  • Viral Load


  • Antigens, Viral
  • Autoantibodies
  • Cytokines
  • Receptors, Cell Surface