In the Absence of Central pre-B Cell Receptor Selection, Peripheral Selection Attempts to Optimize the Antibody Repertoire by Enriching for CDR-H3 Y101

Frontiers in Immunology
Mohamed KhassHarry W Schroeder

Abstract

Sequential developmental checkpoints are used to "optimize" the B cell antigen receptor repertoire by minimizing production of autoreactive or useless immunoglobulins and enriching for potentially protective antibodies. The first and apparently most impactful checkpoint requires μHC to form a functional pre-B cell receptor (preBCR) by associating with surrogate light chain, which is composed of VpreB and λ5. Absence of any of the preBCR components causes a block in B cell development that is characterized by severe immature B cell lymphopenia. Previously, we showed that preBCR controls the amino acid content of the third complementary determining region of the H chain (CDR-H3) by using a VpreB amino acid motif (RDR) to select for tyrosine at CDR-H3 position 101 (Y101). In antibodies bound to antigen, Y101 is commonly in direct contact with the antigen, thus preBCR selection impacts the antigen binding characteristics of the repertoire. In this work, we sought to determine the forces that shape the peripheral B cell repertoire when it is denied preBCR selection. Using bromodeoxyuridine incorporation and evaluation of apoptosis, we found that in the absence of preBCR there is increased turnover of B cells due to increased apoptos...Continue Reading

References

May 29, 1992·Cell·D KitamuraK Rajewsky
Jun 1, 1987·Annals of the Rheumatic Diseases·D A IsenbergA Todd-Pokropek
Jan 1, 1984·Annual Review of Biochemistry·D Eisenberg
Jun 1, 1995·The Journal of Experimental Medicine·R CarsettiM C Lamers
Aug 29, 1997·The Journal of Experimental Medicine·Y J Liu
Jul 7, 1998·Journal of Molecular Biology·A A Bogan, K S Thorn
Jan 6, 1999·Cell·M C Nussenzweig
Mar 13, 2001·Annual Review of Immunology·R R Hardy, K Hayakawa
Dec 12, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·D AllmanR R Hardy
May 30, 2002·Nature Reviews. Immunology·Flavius Martin, John F Kearney
Oct 3, 2002·The Journal of Biological Chemistry·James B PetroWasif N Khan
Sep 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wolfgang SchuhHans-Martin Jäck
Apr 22, 2004·Trends in Immunology·Rudi W Hendriks, Sabine Middendorp
Mar 11, 2005·The Journal of Biological Chemistry·Roberto RangelHector Martinez-Valdez
Jun 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ivaylo I IvanovHarry W Schroeder
Nov 2, 2005·The Journal of Experimental Medicine·Bhaskar SrivastavaDavid Allman
Nov 8, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Robert L SchelonkaHarry W Schroeder
Mar 9, 2007·European Journal of Immunology·Robert L SchelonkaHarry W Schroeder
Aug 20, 2008·The Journal of Experimental Medicine·John B CareyAnn J Feeney
Dec 4, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael ZemlinHarry W Schroeder
Jul 30, 2010·Critical Reviews in Immunology·Harry W SchroederRobert L Schelonka
Apr 17, 2013·The Journal of Experimental Medicine·Andre M ValeHarry W Schroeder
May 6, 2015·The Journal of Clinical Investigation·Fritz Melchers

❮ Previous
Next ❯

Methods Mentioned

BETA
ELISA

Software Mentioned

JMP

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Antibody Repertoire Diversity

Antibody repertoire diversity and its role during natural infection is a prerequisite for molecular and structural elucidation of functionally protective immunity. Discover the latest insights into antibody diversity here.