scholarly journals Positive and negative selection of antigen-specific B cells in transgenic mice expressing variant forms of the VH1 (T15) heavy chain

2000 ◽  
Vol 12 (6) ◽  
pp. 873-885 ◽  
Author(s):  
James J. Kenny ◽  
Eric G. Derby ◽  
Jeffrey A. Yoder ◽  
Shawn A. Hill ◽  
Randy T. Fischer ◽  
...  
Keyword(s):  
B Cells ◽  
Transgenic Mice ◽  
Heavy Chain ◽  
Negative Selection ◽  
Selection Of

scholarly journals Altered BCR and TLR signals promote enhanced positive selection of autoreactive transitional B cells in Wiskott-Aldrich syndrome

2015 ◽  
Vol 212 (10) ◽  
pp. 1663-1677 ◽  
Author(s):  
Nikita S. Kolhatkar ◽  
Archana Brahmandam ◽  
Christopher D. Thouvenel ◽  
Shirly Becker-Herman ◽  
Holly M. Jacobs ◽  
...  
Keyword(s):  
B Cells ◽  
Positive Selection ◽  
B Cell ◽  
Heavy Chain ◽  
High Throughput Sequencing ◽  
Cell Stage ◽  
Wiskott Aldrich Syndrome ◽  
Transitional B Cells ◽  
Selection Of

Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency disorder frequently associated with systemic autoimmunity, including autoantibody-mediated cytopenias. WAS protein (WASp)–deficient B cells have increased B cell receptor (BCR) and Toll-like receptor (TLR) signaling, suggesting that these pathways might impact establishment of the mature, naive BCR repertoire. To directly investigate this possibility, we evaluated naive B cell specificity and composition in WASp-deficient mice and WAS subjects (n = 12). High-throughput sequencing and single-cell cloning analysis of the BCR repertoire revealed altered heavy chain usage and enrichment for low-affinity self-reactive specificities in murine marginal zone and human naive B cells. Although negative selection mechanisms including deletion, anergy, and receptor editing were relatively unperturbed, WASp-deficient transitional B cells showed enhanced proliferation in vivo mediated by antigen- and Myd88-dependent signals. Finally, using both BCR sequencing and cell surface analysis with a monoclonal antibody recognizing an intrinsically autoreactive heavy chain, we show enrichment in self-reactive cells specifically at the transitional to naive mature B cell stage in WAS subjects. Our combined data support a model wherein modest alterations in B cell–intrinsic, BCR, and TLR signals in WAS, and likely other autoimmune disorders, are sufficient to alter B cell tolerance via positive selection of self-reactive transitional B cells.

scholarly journals Positive Selection of Natural Poly-Reactive B Cells in the Periphery Occurs Independent of Heavy Chain Allelic Inclusion

PLoS ONE ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. e0125747
Author(s):  
Ying Xing ◽  
Qiuhe Ji ◽  
Ying Lin ◽  
Meng Fu ◽  
Jixin Gao ◽  
...  
Keyword(s):  
B Cells ◽  
Positive Selection ◽  
Heavy Chain ◽  
Selection Of

scholarly journals Positive and negative selection of T cells in T-cell receptor transgenic mice expressing a bcl-2 transgene.

1994 ◽  
Vol 91 (4) ◽  
pp. 1376-1380 ◽  
Author(s):  
A. Strasser ◽  
A. W. Harris ◽  
H. von Boehmer ◽  
S. Cory
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
T Cell Receptor ◽  
Negative Selection ◽  
Cell Receptor ◽  
Selection Of

scholarly journals Selection of antigen-specific, idiotype-positive B cells in transgenic mice expressing a rearranged M167-mu heavy chain gene.

1991 ◽  
Vol 174 (5) ◽  
pp. 1189-1201 ◽  
Author(s):  
J J Kenny ◽  
C O'Connell ◽  
D G Sieckmann ◽  
R T Fischer ◽  
D L Longo
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
Transgenic Mice ◽  
B Cell ◽  
Flow Cytometric Analysis ◽  
Low Frequency ◽  
Surface Expression ◽  
Chain Gene ◽  
Large Numbers ◽  
Selection Of

Flow cytometric analysis of antigen-specific, idiotype-positive (id+), B cell development in transgenic mice expressing a rearranged M167-mu gene shows that large numbers of phosphocholine (PC)-specific, M167-id+ B cells develop in the spleen and bone marrow of these mice. Random rearrangement of endogenous V kappa genes, in the absence of a subsequent receptor-driven selection, should give rise to equal numbers of T15- and M167-id+ B cells. The observed 100-500-fold amplification of M167-id+ B cells expressing an endogenous encoded V kappa 24]kappa 5 light chain in association with the M167 VH1-id transgene product appears to be an antigen driven, receptor-mediated process, since no amplification of non-PC-binding M167 VH1/V kappa 22, T15-id+ B cells occurs in these mu-only transgenic mice. The selection and amplification of antigen-specific, M167-id+ B cells requires surface expression of the mu transgene product; thus, no enhancement of M167-id+ B cells occurs in the M167 mu delta mem-transgenic mice, which cannot insert the mu transgene product into the B cell membrane. Surprisingly, no selection of PC-specific B cells occurs in M167-kappa-transgenic mice although large numbers of B cells expressing a crossreactive M167-id are present in the spleen and bone marrow of these mice. The failure to develop detectable numbers of M167-id+, PC-specific B cells in M167-kappa-transgenic mice may be due to a very low frequency of M167-VH-region formation during endogenous rearrangement of VH1 to D-JH segments. The somatic generation of the M167 version of a rearranged VH1 gene may occur in less than one of every 10(5) bone marrow B cells, and a 500-fold amplification of this M167-Id+ B cell would not be detectable by flow cytometry even though the anti-PC antibody produced by these B cells is detectable in the serum of M167-kappa-transgenic mice after immunization with PC.

scholarly journals Belimumab promotes negative selection of activated autoreactive B cells in systemic lupus erythematosus patients

JCI Insight ◽  
2018 ◽  
Vol 3 (17) ◽  
Author(s):  
Weiqing Huang ◽  
Tam D. Quach ◽  
Cosmin Dascalu ◽  
Zheng Liu ◽  
Tungming Leung ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
B Cells ◽  
Lupus Erythematosus ◽  
Negative Selection ◽  
Systemic Lupus ◽  
Autoreactive B Cells ◽  
Selection Of

scholarly journals Targeted Expression of Human CD1d in Transgenic Mice Reveals Independent Roles for Thymocytes and Thymic APCs in Positive and Negative Selection of Vα14i NKT Cells

2005 ◽  
Vol 175 (11) ◽  
pp. 7303-7310 ◽  
Author(s):  
Jens Schümann ◽  
Paola Pittoni ◽  
Elena Tonti ◽  
H. Robson MacDonald ◽  
Paolo Dellabona ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Negative Selection ◽  
Nkt Cells ◽  
Targeted Expression ◽  
Selection Of
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