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B cells are exquisitely sensitive to central tolerance and receptor editing induced by ultralow affinity, membrane-bound antigen

Academic Article
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Overview

authors

  • Lang, J.
  • Jackson, M.
  • Teyton, Luc
  • Brunmark, A.
  • Kane, K.
  • Nemazee, David

publication date

  • November 1996

journal

  • Journal of Experimental Medicine  Journal

abstract

  • To assess the sensitivity of B cell tolerance with respect to receptor/autoantigen affinity, we identified low affinity ligands to the 3-83 (anti-major histocompatibility complex class I) antibody and tested the ability of these ligands to induce central and peripheral tolerance in 3-83 transgenic mice. Several class I protein alloforms, including Kbm3 and Dk, showed remarkably low, but detectable, affinity to 3-83. The 3-83 antibody bound Kb with K lambda approximately 2 x 10(5) M-1 and bound 10-fold more weakly to the Kbm3 (K lambda approximately 2 x 10(4) M-1) and Dk antigens. Breeding 3-83 immunoglobulin transgenic mice with mice expressing these ultralow affinity Kbm3 and Dk ligands resulted in virtually complete deletion of the autoreactive B cells from the peripheral lymphoid tissues. These low affinity antigens also induced receptor editing, as measured by elevated RAG mRNA levels in the bone marrow and excess levels of id- variant B cells bearing lambda light chains in the spleen. Reactive class I antigens were also able to mediate deletion of mature B cells when injected into the peritoneal cavity of 3-83 transgenic mice. Although the highest affinity ligand, Kk, was consistently able to induce elimination of the 3-83 peritoneal B cells, the lower affinity ligands were only partially effective. These results demonstrate the remarkable sensitivity of the deletion and receptor-editing mechanisms in immature B cells, and may suggest a higher affinity threshold for deletion of peripheral, mature B cells.

subject areas

  • Animals
  • Autoantigens
  • B-Lymphocytes
  • Bone Marrow
  • Clonal Deletion
  • Cross Reactions
  • H-2 Antigens
  • Histocompatibility Antigens Class I
  • Immune Tolerance
  • Immunoglobulin Idiotypes
  • Ligands
  • Lymphoid Tissue
  • Mice
  • Mice, Transgenic
  • Models, Immunological
  • Peritoneum
  • Protein Binding
  • Receptors, Antigen, B-Cell
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Identity

PubMed Central ID

  • PMC2192881

International Standard Serial Number (ISSN)

  • 0022-1007

Digital Object Identifier (DOI)

  • 10.1084/jem.184.5.1685

PubMed ID

  • 8920858
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Additional Document Info

start page

  • 1685

end page

  • 1697

volume

  • 184

issue

  • 5

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