Chronic GVH prevents anergy in bone marrow self-reactive B cells: a selective increase in post-endoplasmic reticulum processing and trafficking to the cell surface of autoreactive IgM receptors

Autor: Fangqi Chen, Debra K. Shivers, Terri H. Finkel, Robert A. Eisenberg, Nili Feuerstein
Rok vydání: 2003
Předmět:
Adoptive cell transfer
Graft vs Host Disease
Autoimmunity
Antigen-Antibody Complex
Receptors
Fc
Lymphocyte Activation
Mice
Immunology and Allergy
Receptor
B-Lymphocytes
Membrane Glycoproteins
Immunoglobulin mu-Chains
ER retention
General Medicine
Flow Cytometry
Adoptive Transfer
Protein Transport
Hexosaminidases
medicine.anatomical_structure
Blotting
Western
Immunology
Naive B cell
Receptors
Antigen
B-Cell
Bone Marrow Cells
Enzyme-Linked Immunosorbent Assay
Mice
Transgenic
chemical and pharmacologic phenomena
Biology
Antigen
Antigens
CD
medicine
Animals
B cell
Autoantibodies
Clonal Anergy
Receptors
IgE
Endoplasmic reticulum
Histocompatibility Antigens Class II
CD24 Antigen
Immunoglobulin D
Mice
Inbred C57BL
Immunoglobulin M
Chronic Disease
biology.protein
Leukocyte Common Antigens
Muramidase
B7-2 Antigen
Protein Processing
Post-Translational
Spleen
Zdroj: International Immunology. 15:975-985
ISSN: 1460-2377
DOI: 10.1093/intimm/dxg097
Popis: B cell autoreactivity is a component of chronic graft versus host (GVH) disease in humans and mice. Chronic GVH driven by I-A disparity results in loss of B cell tolerance in Ig/sHEL tolerant mice. In these mice, B cell anergy is characterized by down-modulation of sIgM mediated by intracellular retention in the endoplasmic reticulum (ER) and/or a block in post-ER processing of IgM receptors. Here, we report that GVH induces a selective increase in post-ER processing of the micro chain and trafficking to the cell surface of IgM receptors in B cells that bind HEL self-antigen. The increase in sIgM was detectable as early as 6 days post-GVH, before the appearance of circulating autoantibodies, and was particularly prominent in B cells that up-regulated surface I-A. A further increase in sIgM was found at later time points, along with circulating anti-HEL autoantibodies and a marked decrease in serum-free HEL, but no significant change in the amounts of HEL bound to B cells in vivo. These findings suggest that (i) abrogation of ER retention of IgM receptors in self-reactive B cells is an early event triggered by allogeneic T cells and (ii) at later stages of GVH disease the appearance of autoantibodies reduces the availability of free autoantigen, which may further escalate anergy escape of self-reactive B cells, and lead to exacerbation and perpetuation of autoimmunity.
Databáze: OpenAIRE
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