Molecular Regulation of VH Gene Replacement in Human Immature B Cells

  • Zhang, Zhixin, (PI)

Project: Research project

Description

DESCRIPTION (provided by applicant): Although the concept of VH replacement has a lengthy history, the natural occurrence and molecular basis of VH replacement in human B cells have just been realized from our recent studies. VH replacement occurs through RAG-mediated secondary recombination involving the cryptic RSS (cRSS) within the rearranged VHDJH region and the 23 bp RSS from an upstream VH gene. VH replacement occurs in bone marrow immature B cells during human B cell development and contributes to about 5% of the periphery B cell repertoire in humans. Our recent studies showed that the frequencies of VH replacement products are significantly elevated in autoimmune diseases and in IgH genes encoding anti-viral antibodies, suggesting an unrealized important function of VH replacement. The current proposal focuses on the molecular regulation of VH replacement in human immature B cells. We found that crosslinking BCR strongly induces VH replacement in the EU12
StatusFinished
Effective start/end date4/1/083/31/14

Funding

  • National Institutes of Health: $294,030.00
  • National Institutes of Health: $291,090.00
  • National Institutes of Health: $290,000.00
  • National Institutes of Health: $297,000.00
  • National Institutes of Health: $291,090.00

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B-Lymphoid Precursor Cells
B-Lymphocytes
Genes
Viral Antibodies
Natural History
Genetic Recombination
Autoimmune Diseases
Anti-Idiotypic Antibodies
Bone Marrow

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)