CD98 is a potential target for ablating B cell clonal expansion and autoantibody in multiple sclerosis

J Neuroimmunol. 2014 Sep 15;274(1-2):230-3. doi: 10.1016/j.jneuroim.2014.06.015. Epub 2014 Jun 26.

Abstract

Current B cell-directed therapies for multiple sclerosis impact multiple B cell functions. CD98hc enables B cell clonal expansion and antibody production. I probed the relative importance of autoantibody secretion vs. other B cell functions in MS and targeted CD98hc as a possible therapeutic strategy. I report that the loss of CD98hc function in B cells largely prevents autoantibody production while preserving antigen-presenting and T cell-directing capacities. Mice lacking CD98hc in B cells are protected from EAE; importantly this is overcome with autoantibody-containing plasma. Thus CD98hc blockade is a possible avenue to treat MS by inhibiting clonal expansion and autoantibody.

Keywords: Autoantibody; B cell; CD98; Clonal expansion; EAE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Fusion Regulatory Protein-1 / immunology*
  • Humans
  • Mice
  • Mice, Mutant Strains
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / immunology*
  • Myelin-Oligodendrocyte Glycoprotein / immunology
  • Myelin-Oligodendrocyte Glycoprotein / pharmacology
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology

Substances

  • Autoantibodies
  • Fusion Regulatory Protein-1
  • MOG protein, human
  • Myelin-Oligodendrocyte Glycoprotein
  • Recombinant Proteins