From systemic T cell self-reactivity to organ-specific autoimmune disease via immunoglobulins

Immunity. 1999 Apr;10(4):451-61. doi: 10.1016/s1074-7613(00)80045-x.


Rheumatoid arthritis is a common and debilitating autoimmune disease whose cause and mechanism remain a mystery. We recently described a T cell receptor transgenic mouse model that spontaneously develops a disease with most of the clinical, histological, and immunological features of rheumatoid arthritis in humans. Disease development in K/BxN mice is initiated by systemic T cell self-reactivity; it requires T cells, as expected, but B cells are also needed, more surprisingly. Here, we have identified the role of B cells as the secretion of arthritogenic immunoglobulins. We suggest that a similar scenario may unfold in some other arthritis models and in human patients, beginning with pervasive T cell autoreactivity and ending in immunoglobulin-provoked joint destruction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibody Specificity / genetics
  • Antigen Presentation / genetics
  • Arthritis, Rheumatoid / genetics
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Disease Models, Animal
  • Epitopes, B-Lymphocyte / genetics
  • Epitopes, B-Lymphocyte / immunology
  • Humans
  • Immunoglobulins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mice, Transgenic
  • Organ Specificity / genetics
  • Organ Specificity / immunology
  • T-Lymphocytes / immunology*


  • Epitopes, B-Lymphocyte
  • Immunoglobulins