Selective Maturation of VH12 B Cells in the Spleen Enriches for Anti-Phosphatidyl Choline B Cells: Evidence for Receptor Editing

2000 ◽  
pp. 77-86 ◽  
Author(s):  
C. Tatu ◽  
S. H. Clarke
Keyword(s):  
B Cells ◽  
Phosphatidyl Choline ◽  
Receptor Editing

scholarly journals Enforced Bcl-2 Expression Inhibits Antigen-mediated Clonal Elimination of Peripheral B Cells in an Antigen Dose–dependent Manner and Promotes Receptor Editing in Autoreactive, Immature B Cells

1997 ◽  
Vol 186 (9) ◽  
pp. 1513-1522 ◽  
Author(s):  
Julie Lang ◽  
B. Arnold ◽  
G. Hammerling ◽  
Alan W. Harris ◽  
Stanley Korsmeyer ◽  
...  
Keyword(s):  
B Cells ◽  
Tolerance Induction ◽  
Antigen Expression ◽  
Dependent Manner ◽  
Receptor Editing ◽  
B Cell Tolerance ◽  
Antigen Dose ◽  
Central Tolerance ◽  
Self Tolerance ◽  
Immature B Cells

The mechanisms that establish immune tolerance in immature and mature B cells appear to be distinct. Membrane-bound autoantigen is thought to induce developmental arrest and receptor editing in immature B cells, whereas mature B cells have shortened lifespans when exposed to the same stimulus. In this study, we used Eμ–bcl-2-22 transgenic (Tg) mice to test the prediction that enforced expression of the Bcl-2 apoptotic inhibitor in B cells would rescue mature, but not immature, B cells from tolerance induction. To monitor tolerance to the natural membrane autoantigen H-2Kb, we bred 3–83μδ (anti-Kk,b) Ig Tg mice to H-2b mice or to mice expressing transgene-driven Kb in the periphery. In 3–83μδ/bcl-2 Tg mice, deletion of autoreactive B cells induced by peripheral Kb antigen expression in the liver (MT-Kb Tg) or epithelia (KerIV-Kb Tg), was partly or completely inhibited, respectively. Furthermore, Bcl-2 protected peritoneal B-2 B cells from deletion mediated by acute antigen exposure, but this protection could be overcome by higher antigen dose. In contrast to its ability to block peripheral self-tolerance, Bcl-2 overexpression failed to inhibit central tolerance induced by bone marrow antigen expression, but instead, enhanced the receptor editing process. These studies indicate that apoptosis plays distinct roles in central and peripheral B cell tolerance.

scholarly journals Normal mouse peritoneum contains a large population of Ly-1+ (CD5) B cells that recognize phosphatidyl choline. Relationship to cells that secrete hemolytic antibody specific for autologous erythrocytes.

1988 ◽  
Vol 168 (2) ◽  
pp. 687-698 ◽  
Author(s):  
T J Mercolino ◽  
L W Arnold ◽  
L A Hawkins ◽  
G Haughton
Keyword(s):  
B Cells ◽  
Cell Surface ◽  
Phosphatidyl Choline ◽  
Large Population ◽  
In Vivo Studies ◽  
Antigen Specificity ◽  
Adult Mice ◽  
Large Numbers

We have found that, in the peritoneums of normal adult mice, 5-15% of lymphocytes bind a fluorescent liposome probe. In ontogeny, cells with this specificity were shown to appear by 8 d after birth, and increase to the adult frequency by 2-3 wk. Some older mice contain an expanded population of these cells. We have shown that liposome binding occurs by cell surface IgM recognizing the common membrane phospholipid, phosphatidyl choline (PtC). Virtually all of these PtC-specific cells bear the cell surface marker Ly-1. Our results indicate that roughly 1 in 10 peritoneal Ly-1+ B cells has this single specificity. We have found that the precursors to all the cells that form plaques on protease-treated autologous erythrocytes (BrMRBC) are included in the PtC-specific population and can be isolated by FACS. We believe this is the first report of sorting large numbers of B cells with a single antigen specificity from normal, unimmunized animals. This method will allow for in vitro and in vivo studies of differentiative and proliferative properties of Ly-1+ B cells, which may help define their role in development and disease.

scholarly journals Reduced receptor editing in lupus-prone MRL/lpr mice

2007 ◽  
Vol 204 (12) ◽  
pp. 2853-2864 ◽  
Author(s):  
Jennifer L. Lamoureux ◽  
Lisa C. Watson ◽  
Marie Cherrier ◽  
Patrick Skog ◽  
David Nemazee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Messenger Rna ◽  
Immunoglobulin M ◽  
Considerable Proportion ◽  
Receptor Editing ◽  
Cell Tolerance ◽  
B Cell Tolerance ◽  
Immature B Cells

The initial B cell repertoire contains a considerable proportion of autoreactive specificities. The first major B cell tolerance checkpoint is at the stage of the immature B cell, where receptor editing is the primary mode of eliminating self-reactivity. The cells that emigrate from the bone marrow have a second tolerance checkpoint in the transitional compartment in the spleen. Although it is known that the second checkpoint is defective in lupus, it is not clear whether there is any breakdown in central B cell tolerance in the bone marrow. We demonstrate that receptor editing is less efficient in the lupus-prone strain MRL/lpr. In an in vitro system, when receptor-editing signals are given to bone marrow immature B cells by antiidiotype antibody or after in vivo exposure to membrane-bound self-antigen, MRL/lpr 3-83 transgenic immature B cells undergo less endogenous rearrangement and up-regulate recombination activating gene messenger RNA to a lesser extent than B10 transgenic cells. CD19, along with immunoglobulin M, is down-regulated in the bone marrow upon receptor editing, but the extent of down-regulation is fivefold less in MRL/lpr mice. Less efficient receptor editing could allow some autoreactive cells to escape from the bone marrow in lupus-prone mice, thus predisposing to autoimmunity.

scholarly journals Receptor Editing Can Lead to Allelic Inclusion and Development of B Cells That Retain Antibodies Reacting with High Avidity Autoantigens

2005 ◽  
Vol 175 (8) ◽  
pp. 5067-5076 ◽  
Author(s):  
Sucai Liu ◽  
Maria-Gabriela Velez ◽  
Jessica Humann ◽  
Sarah Rowland ◽  
Frank J. Conrad ◽  
...  
Keyword(s):  
B Cells ◽  
High Avidity ◽  
Receptor Editing

scholarly journals Light chain editors of anti-DNA receptors in human B cells

2014 ◽  
Vol 211 (2) ◽  
pp. 357-364 ◽  
Author(s):  
Olga Kalinina ◽  
Yue Wang ◽  
Kevin Sia ◽  
Marko Radic ◽  
Pierre-André Cazenave ◽  
...  
Keyword(s):  
B Cells ◽  
Dna Binding ◽  
Mouse Models ◽  
Protein Sequences ◽  
Receptor Editing ◽  
Transgenic Mouse Models ◽  
Human B Cells ◽  
Self Tolerance ◽  
V Genes ◽  
Complementarity Determining Region

Receptor editing is a mechanism of self-tolerance used in newly generated B cells. The expressed heavy (H) or light (L) chain of an autoreactive receptor is replaced by upstream V genes which eliminate or modify autoreactivity. Editing of anti-DNA receptors has been characterized in anti-DNA transgenic mouse models including 3H9, 3H9/56R, and their revertant 3H9GL. Certain L chains, termed editors, rescue anti-DNA B cells by neutralizing or modifying DNA binding of the H chain. This editing mechanism acts on the natural H chain repertoire; endogenous H chains with anti-DNA features are expressed primarily in combination with editor L chains. We ask whether a similar set of L chains exists in the human repertoire, and if so, do they edit H chains with anti-DNA signatures? We compared the protein sequences of mouse editors to all human L chains and found several human L chains similar to mouse editors. These L chains diminish or veto anti-DNA binding when expressed with anti-DNA H chains. The human H chains expressed with these L chains also have relatively high arginine (Arg) content in the H chain complementarity determining region (H3), suggesting that receptor editing plays a role in establishing tolerance to DNA in humans.

scholarly journals B cells are exquisitely sensitive to central tolerance and receptor editing induced by ultralow affinity, membrane-bound antigen.

1996 ◽  
Vol 184 (5) ◽  
pp. 1685-1697 ◽  
Author(s):  
J Lang ◽  
M Jackson ◽  
L Teyton ◽  
A Brunmark ◽  
K Kane ◽  
...  
Keyword(s):  
B Cells ◽  
Transgenic Mice ◽  
Peripheral Tolerance ◽  
Class I ◽  
Lymphoid Tissues ◽  
Mrna Levels ◽  
Receptor Editing ◽  
Central Tolerance ◽  
Affinity Ligands ◽  
Affinity Ligand

To assess the sensitivity of B cell tolerance with respect to receptor/autoantigen affinity, we identified low affinity ligands to the 3-83 (anti-major histocompatibility complex class I) antibody and tested the ability of these ligands to induce central and peripheral tolerance in 3-83 transgenic mice. Several class I protein alloforms, including Kbm3 and Dk, showed remarkably low, but detectable, affinity to 3-83. The 3-83 antibody bound Kb with K lambda approximately 2 x 10(5) M-1 and bound 10-fold more weakly to the Kbm3 (K lambda approximately 2 x 10(4) M-1) and Dk antigens. Breeding 3-83 immunoglobulin transgenic mice with mice expressing these ultralow affinity Kbm3 and Dk ligands resulted in virtually complete deletion of the autoreactive B cells from the peripheral lymphoid tissues. These low affinity antigens also induced receptor editing, as measured by elevated RAG mRNA levels in the bone marrow and excess levels of id- variant B cells bearing lambda light chains in the spleen. Reactive class I antigens were also able to mediate deletion of mature B cells when injected into the peritoneal cavity of 3-83 transgenic mice. Although the highest affinity ligand, Kk, was consistently able to induce elimination of the 3-83 peritoneal B cells, the lower affinity ligands were only partially effective. These results demonstrate the remarkable sensitivity of the deletion and receptor-editing mechanisms in immature B cells, and may suggest a higher affinity threshold for deletion of peripheral, mature B cells.

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