A role for membrane IgD in the tolerance of pathological human rheumatoid factor B cells.
Under non-autoimmune conditions, rheumatoid factor (RF) B cells coexist peacefully with their antigen (IgG), or can be transiently activated during secondary immune responses because they can present xenoantigens to specific T cells captured in immune complex form. Such a situation should lead to affinity maturation of RF B cells and potentially dangerous production of high-affinity RF. We used two lines of transgenic mice expressing a somatically mutated pathological human RF in presence (IgM and IgD) or in absence (IgM only) of surface IgD, and confirm that RF B cell tolerance can result from an antigen-induced specific, but incomplete, deletion of naive RF B cells after antigen encounter. This deletion mainly concerns immature, transitional B cells. On the contrary, mature, IgM- and IgD-expressing RF B cells are resistant to such a deletion. These IgM and IgD RF B cells are functional and activable through both B cell receptor dependent (anti-IgM) and independent (LPS) pathways, but they are not fully responsive to human IgG either in vivo or in vitro. Taken together, these results suggest that another mechanism could be involved in the silencing of mature naive IgM and IgD RF B cells.
Soulas
Pauline
P
Laboratoire d'Immunopathologie, Institut d'Hématologie et d'Immunologie, Strasbourg, France.
Koenig-Marrony
Severine
S
Julien
Sylvie
S
Knapp
Anne-Marie
AM
Garaud
Jean-Claude
JC
Pasquali
Jean-Louis
JL
Martin
Thierry
T
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D017635:Clonal Anergy / Q000276:immunology; D017637:Clonal Deletion / Q000276:immunology*; D005803:Genes, Immunoglobulin; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007072:Immunoglobulin D / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D012217:Rheumatoid Factor / Q000235:genetics / Q000276:immunology*; D019076:Transgenes
D007072:Immunoglobulin D; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; D012217:Rheumatoid Factor