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Structural and mechanistic insight i...

Bankovich, Alexander John.

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Structural and mechanistic insight into pre B cell receptor signaling and recognition.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Structural and mechanistic insight into pre B cell receptor signaling and recognition./
Author:	Bankovich, Alexander John.
Description:	118 p.
Notes:	Source: Dissertation Abstracts International, Volume: 66-11, Section: B, page: 5885.
Contained By:	Dissertation Abstracts International66-11B.
Subject:	Health Sciences, Immunology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3197405
ISBN:	9780542431029

Structural and mechanistic insight into pre B cell receptor signaling and recognition.
Bankovich, Alexander John.

Structural and mechanistic insight into pre B cell receptor signaling and recognition. - 118 p.

Source: Dissertation Abstracts International, Volume: 66-11, Section: B, page: 5885.

Thesis (Ph.D.)--Stanford University, 2006.

A developing B cell possesses a regulatory step to ensure that its highly-variable, randomly-rearranged receptor expressed on the cell surface is functional, yet not autoreactive. Following heavy chain rearrangement, lambda5 and VpreB, a heterodimeric complex of two germline-encoded (i.e. invariant) proteins termed "surrogate light chain" (SLC), pair with the heavy chain to form a surface-expressed preB Cell Receptor (preBCR). The pairing of SLC with heavy chain occurs for about half of the rearranged heavy chains, leading to clonal expansion through three to five rounds of cell division. If a heavy chain does not bind, clonal expansion does not occur, leading to a drastic under-representation of that heavy chain in the mature B cell population. It is the our goal to elucidate the structural determinants by which the SLC is able to "sense" the identity of a heavy chain and regulate the antibody repertoire.

ISBN: 9780542431029Subjects--Topical Terms:

1017716
Health Sciences, Immunology.

Structural and mechanistic insight into pre B cell receptor signaling and recognition.
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020 $a 9780542431029
035 $a (UnM)AAI3197405
035 $a AAI3197405
040 $a UnM $c UnM
100 1 $a Bankovich, Alexander John. $3 1909487
245 1 0 $a Structural and mechanistic insight into pre B cell receptor signaling and recognition.
300 $a 118 p.
500 $a Source: Dissertation Abstracts International, Volume: 66-11, Section: B, page: 5885.
500 $a Adviser: K. Christopher Garcia.
502 $a Thesis (Ph.D.)--Stanford University, 2006.
520 $a A developing B cell possesses a regulatory step to ensure that its highly-variable, randomly-rearranged receptor expressed on the cell surface is functional, yet not autoreactive. Following heavy chain rearrangement, lambda5 and VpreB, a heterodimeric complex of two germline-encoded (i.e. invariant) proteins termed "surrogate light chain" (SLC), pair with the heavy chain to form a surface-expressed preB Cell Receptor (preBCR). The pairing of SLC with heavy chain occurs for about half of the rearranged heavy chains, leading to clonal expansion through three to five rounds of cell division. If a heavy chain does not bind, clonal expansion does not occur, leading to a drastic under-representation of that heavy chain in the mature B cell population. It is the our goal to elucidate the structural determinants by which the SLC is able to "sense" the identity of a heavy chain and regulate the antibody repertoire.
520 $a We have expressed soluble preBCR in a Fab-like form. Full-length, soluble preBCR dimerizes with a dependence on the "unique regions" of the molecule and is consistent with homotypic aggregation as the means of signaling. We have shown that the preBCR does not appear able to bind to cognate antigen (ovalbumin) when the specificity for antigen resides entirely in the complementarity determining region 3 (CDR3) of the heavy chain.
520 $a We have solved the crystal structure of preBCR to a resolution of 2.8A. The obligate heterodimer of lambda5 and VpreB forms an extended interaction with the heavy chain in a manner reminiscent of the heavy/light pairing of a Fab fragment of an antibody. However, the SLC structure reveals a striking difference in the topology of the beta strands in the Immunoglobulin folds. The region of VpreB analogous to the CDR3 of the light chain, termed the "unique region" masks the CDR3 of the heavy chain, providing a significant steric barrier to antigen recognition. The interactions of the surrogate light chain with rearranged heavy chain, in particular the CDR3-H, indicate how the surrogate light chain can probe CDR3-H sequence to regulate heavy chain selection. These studies have given insight into preBCR signaling, antigen recognition, and heavy chain repertoire selection mechanisms.
590 $a School code: 0212.
650 4 $a Health Sciences, Immunology. $3 1017716
650 4 $a Chemistry, Biochemistry. $3 1017722
650 4 $a Biophysics, General. $3 1019105
690 $a 0982
690 $a 0487
690 $a 0786
710 2 0 $a Stanford University. $3 754827
773 0 $t Dissertation Abstracts International $g 66-11B.
790 1 0 $a Garcia, K. Christopher, $e advisor
790 $a 0212
791 $a Ph.D.
792 $a 2006
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3197405