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B cell positive selection by soluble self-antigen.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2002 Oct 15; Vol. 169 (8), pp. 4198-204. - Publication Year :
- 2002
-
Abstract
- It is well established that autoreactive B cells undergo negative selection. This stands in paradox with the high frequency of so-called natural autoreactive B cells producing low affinity polyreactive autoantibodies with recurrent specificities, suggesting that these B cells are selected on the basis of their autoreactivity. We previously described two transgenic mouse lines (with and without IgD) producing a human natural autoantibody (nAAb) that binds ssDNA and human Fcgamma. In the absence of human IgG, nAAb-transgenic B cells develop normally. By crossing these mice with animals expressing knockin chimeric IgG with the human Fcgamma, we now show that the constitutive expression of chimeric IgG promotes the increase of nAAb-expressing B cells. This positive selection is critically dependent on the presence of IgD, occurs in the spleen, and concerns all mature B cell subsets, with a relative preferential enrichment of marginal zone B cells. These data support the view that soluble self-Ags can result in positive clonal selection.
- Subjects :
- Animals
Autoantibodies biosynthesis
Autoantibodies genetics
Autoantigens biosynthesis
B-Lymphocyte Subsets metabolism
Cell Differentiation genetics
Cell Differentiation immunology
Cells, Cultured
Clonal Anergy genetics
Epitopes, B-Lymphocyte physiology
Humans
Immunity, Innate genetics
Immunoglobulin D biosynthesis
Immunoglobulin D genetics
Immunoglobulin G genetics
Immunoglobulin G physiology
Immunoglobulin M biosynthesis
Immunoglobulin M genetics
Mice
Mice, Inbred C57BL
Mice, Transgenic
Receptors, Antigen, B-Cell physiology
Recombinant Fusion Proteins genetics
Recombinant Fusion Proteins physiology
Solubility
Spleen cytology
Spleen immunology
Spleen metabolism
Autoantigens immunology
B-Lymphocyte Subsets cytology
B-Lymphocyte Subsets immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 169
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 12370349
- Full Text :
- https://doi.org/10.4049/jimmunol.169.8.4198