Positive selection of anti-thy-1 autoreactive B-1 cells and natural serum autoantibody production independent from bone marrow B cell development.
A natural serum autoantibody specific for the Thy-1 glycoprotein (anti-Thy-1 autoantibody [ATA]) is produced by B-1 cells that are positively selected by self-antigen. Here, using ATA micro kappa transgenic mice we show that cells with this B cell receptor are negatively selected during bone marrow (BM) development. In a Thy-1 null environment, BM ATA B cells progress to a normal follicular stage in spleen. However, in a self-antigen-positive environment, development is arrested at an immature stage in the spleen, concomitant with induction of CD5. Such cells are tolerant and short-lived, different from B-1. Nonetheless, ATA-positive selection was evident by self-antigen-dependent high serum ATA production, comprising approximately 90% of serum immunoglobulin M in ATA micro kappa mice. Splenectomy did not eliminate ATA production and transfer of tolerant splenic B cells did not induce it. These findings demonstrate that B-1 positive selection, resulting in the production of natural serum ATA, arises independently from the major pathway of BM B cell development and selection.
Hayakawa
Kyoko
K
Fox Chase Cancer Center, Philadelphia, PA 19111, USA. K_Hayakawa@fccc.edu
Asano
Masanao
M
Shinton
Susan A
SA
Gui
Ming
M
Wen
Li-Jun
LJ
Dashoff
Joni
J
Hardy
Richard R
RR
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis* / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D018956:CD5 Antigens / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D002465:Cell Movement; D005434:Flow Cytometry; D007108:Immune Tolerance; D007075:Immunoglobulin M / Q000032:analysis / Q000276:immunology; D016130:Immunophenotyping; D051379:Mice; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013156:Splenectomy; D018800:Thy-1 Antigens / Q000032:analysis / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D018956:CD5 Antigens; D007075:Immunoglobulin M; D018800:Thy-1 Antigens