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Reciprocal regulation of B cell anti...

Skrzypczynska, Katarzyna Maria.

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Reciprocal regulation of B cell antigen receptor signaling by CD148 and Csk.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Reciprocal regulation of B cell antigen receptor signaling by CD148 and Csk./
Author:	Skrzypczynska, Katarzyna Maria.
Description:	217 p.
Notes:	Source: Dissertation Abstracts International, Volume: 77-07(E), Section: B.
Contained By:	Dissertation Abstracts International77-07B(E).
Subject:	Immunology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10027452
ISBN:	9781339526706

Reciprocal regulation of B cell antigen receptor signaling by CD148 and Csk.
Skrzypczynska, Katarzyna Maria.

Reciprocal regulation of B cell antigen receptor signaling by CD148 and Csk. - 217 p.

Source: Dissertation Abstracts International, Volume: 77-07(E), Section: B.

Thesis (Ph.D.)--University of California, San Francisco, 2015.

B cell antigen receptor (BCR) signaling is tightly regulated by the opposing actions of receptor-like protein tyrosine phosphatases (RPTPs) and C-terminal Src kinase (Csk). The RPTPs CD45 and CD148 positively regulate BCR signaling through their actions on Src-family kinases (SFKs) and have redundant functions in conventional (B2) B cell signaling and activation. However, we found that IgM production in response to T cell-independent type 2 antigens, which is mediated in large part by B1 B cells, was deficient in mice lacking CD148. B1 B cells, which normally express high levels of CD148 compared with B2 B cells, were uniquely affected by the loss of CD148, resulting in impaired proliferation, antibody production, BCR repertoire development, and BCR signaling. Analysis of proximal BCR signaling in mice deficient in CD148 or the SFK Lyn revealed that Lyn has a predominantly positive regulatory role in B1 B cell BCR signaling, compared with its dominant negative regulatory role observed in B2 B cells. This suggests that BCR signaling circuitry is wired differently in B1 B cells resulting in a requirement for positive regulation of Lyn by CD148 for full BCR signaling.

ISBN: 9781339526706Subjects--Topical Terms:

611031
Immunology.

Reciprocal regulation of B cell antigen receptor signaling by CD148 and Csk.
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100 1 $a Skrzypczynska, Katarzyna Maria. $3 3192628
245 1 0 $a Reciprocal regulation of B cell antigen receptor signaling by CD148 and Csk.
300 $a 217 p.
500 $a Source: Dissertation Abstracts International, Volume: 77-07(E), Section: B.
500 $a Adviser: Arthur Weiss.
502 $a Thesis (Ph.D.)--University of California, San Francisco, 2015.
520 $a B cell antigen receptor (BCR) signaling is tightly regulated by the opposing actions of receptor-like protein tyrosine phosphatases (RPTPs) and C-terminal Src kinase (Csk). The RPTPs CD45 and CD148 positively regulate BCR signaling through their actions on Src-family kinases (SFKs) and have redundant functions in conventional (B2) B cell signaling and activation. However, we found that IgM production in response to T cell-independent type 2 antigens, which is mediated in large part by B1 B cells, was deficient in mice lacking CD148. B1 B cells, which normally express high levels of CD148 compared with B2 B cells, were uniquely affected by the loss of CD148, resulting in impaired proliferation, antibody production, BCR repertoire development, and BCR signaling. Analysis of proximal BCR signaling in mice deficient in CD148 or the SFK Lyn revealed that Lyn has a predominantly positive regulatory role in B1 B cell BCR signaling, compared with its dominant negative regulatory role observed in B2 B cells. This suggests that BCR signaling circuitry is wired differently in B1 B cells resulting in a requirement for positive regulation of Lyn by CD148 for full BCR signaling.
520 $a Using novel tools recently generated in the lab, we also investigated the effects of selective chemical inhibition of Csk in primary mouse follicular B cells. This preliminary work reveals mechanisms for the negative regulation of BCR signaling by Csk independent of BCR engagement.
590 $a School code: 0034.
650 4 $a Immunology. $3 611031
650 4 $a Health sciences. $3 3168359
650 4 $a Cellular biology. $3 3172791
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710 2 $a University of California, San Francisco. $b Biomedical Sciences. $3 1263090
773 0 $t Dissertation Abstracts International $g 77-07B(E).
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791 $a Ph.D.
792 $a 2015
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10027452