GSBS Student Publications
Title
xid mice reveal the interplay of homeostasis and Bruton's tyrosine kinase-mediated selection at multiple stages of B cell development
GSBS Program
Biochemistry & Molecular Pharmacology
Publication Date
2001-11-22
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Molecular Genetics and Microbiology; Department of Physiology
Document Type
Article
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
Human X-linked agammaglobulinemia (XLA) and murine X-linked immune defect (XID) are both immunodeficiencies mediated by mutations in Bruton's tyrosine kinase (Btk), yet the developmental stage(s) affected remain controversial. To further refine the placement of the XID defect(s), we used bromodeoxyuridine labeling to determine turnover, production and transition rates of developing B cell subsets in normal, xid and xid mice expressing a human Bcl-2 transgene (xid/bcl-2). We find the xid mutation manifest at two stages of B cell development. The first is early, reducing pre-B cell production by restricting pro-B to pre-B cell transit. Surprisingly, this impairment is offset by increased survival of cells progressing from the pre- to immature B cell pool, suggesting that Btk-independent homeostatic mechanisms act to maintain this compartment. The second point of action is late, substantially reducing mature B cell production. Together, these findings reconcile apparent discrepancies in the developmental stage affected by the murine versus human lesions and suggest previously unappreciated homeostatic processes that act at the pre-B to immature B cell transition. Finally, Btk likely functions differently at these two checkpoints, since ectopic Bcl-2 expression fails to directly complement the early xid lesion, yet reverses the defect impeding final B cell maturation.
DOI of Published Version
10.1093/intimm/13.12.1501
Source
Int Immunol. 2001 Dec;13(12):1501-14.
Journal/Book/Conference Title
International immunology
Related Resources
PubMed ID
11717191
Repository Citation
Cancro MP, Sah AP, Levy SL, Allman DM, Schmidt MR, Woodland RT. (2001). xid mice reveal the interplay of homeostasis and Bruton's tyrosine kinase-mediated selection at multiple stages of B cell development. GSBS Student Publications. https://doi.org/10.1093/intimm/13.12.1501. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/181