Proliferation of Ly-1 B cells in autoimmune NZB and (NZB x NZW)F1 mice

Eur J Immunol. 1987 Jun;17(6):809-14. doi: 10.1002/eji.1830170612.

Abstract

Spontaneous autoimmune disease in NZB and (NZB x NZW)F1 (B/W) mice is associated with a spectrum of lymphoproliferative abnormalities, but the relationship between autoimmunity and lymphoproliferation is poorly understood. Lymphomas occur commonly in NZB mice, but they appear to be rare in B/W mice, perhaps because B/W mice die of murine lupus before the lymphomas are evident. We recently reported that autoimmune disease in B/W mice could be reversed by weekly treatment with monoclonal antibodies to the L3T4 antigen on "helper/inducer" T cells. This has enabled us to examine the evolution of lymphoproliferation in B/W mice that survive beyond the usual life span, both in long-term survivors of treatment with anti-L3T4 and in the occasional B/W mouse that spontaneously survives beyond 1 year of age. We find that all of these mice develop marked proliferation of a distinct subpopulation of B cells that express the Ly-1 antigen in low density. These Ly-1+ B cells account for a 2-10-fold increase in the number of splenic, lymph node and peripheral blood lymphocytes. The Ly-1 B cells in individual mice are restricted in their expression of immunoglobulin light chains, suggesting a clonal origin. NZB mice. develop similar proliferation of Ly-1 B cells, suggesting that this is due to underlying genetic and/or viral factors in NZB and B/W mice, and that it is not the result of treatment with anti-L3T4. Although recent studies have implicated Ly-1 B cells in the production of autoantibodies, proliferation of Ly-1 B cells in B/W mice was not associated with production of anti-DNA antibodies or with any paraprotein.

Publication types

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

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use
  • Antibody Specificity
  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Ly / immunology*
  • Antigens, Surface / immunology
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / mortality
  • B-Lymphocytes / immunology*
  • DNA / immunology
  • Female
  • Flow Cytometry / methods
  • Immunoglobulin Light Chains / genetics
  • Lymph Nodes / cytology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred NZB / immunology*
  • Mice, Inbred Strains
  • Spleen / cytology
  • T-Lymphocytes, Helper-Inducer / immunology

Substances

  • Antibodies
  • Antibodies, Monoclonal
  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Ly
  • Antigens, Surface
  • Immunoglobulin Light Chains
  • DNA