期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 197, 期 1, 页码 87-99出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20021459
关键词
B-1; ATA; CD5; IgM; Thy-1
资金
- NIAID NIH HHS [R01 AI40946, R01 AI049335, R01 AI040946, R01 AI026782, R01 AI49335, R01 AI26782] Funding Source: Medline
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 ATAmukappa 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 similar to90% of serum immunoglobulin M in ATAmukappa 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.
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