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- Title
Defects in early B-cell development: comparing the consequences of abnormalities in pre-BCD signaling in the human and the mouse.
- Authors
Conley, Mary Ellen; Rohrer, Jurg; Rapalus, Lisa; Boylin, Elizabeth C.; Minegishi, Yoshiyuki
- Abstract
Summary: Patients with genetic defects in B-cell development provide an unusual opportunity to dissect the requirements for normal B-cell maturation. It is striking that all of the known genetic defects that result in a failure of B-cell development involve signaling through the pre-B-cell receptor (pre-BCR). Approximately 85% of affected patients are males with mutations in the X chromosome-encoded cytoplasmic tyrosine kinase Btk. Preliminary experiments using stem cell transplants and retroviral-mediated gene therapy in Btk-deficient mice suggest that it may be relatively easy to correct serum immunoglobulins but harder to correct antibody production to T-cell independent antigens in this disorder. About 3-6% of patients with defects in B-cell development have deletions or critical base pair substitutions in the μ constant region gene. Patients with defects in Igα λ5 and B-cell linker protein (BLNK) have also been described. All of these patients have a block at the pro-B to pre-B-cell transition. Defects in Btk, λ5 and BLNK result in a more severe phenotype in the human compared to the mouse. These findings suggest that requirements for signaling through the pre-BCR are more stringent in the human compared to the mouse. Possible explanations for this observation are discussed.
- Publication
Immunological Reviews, 2000, Vol 178, Issue 1, p75
- ISSN
0105-2896
- Publication type
Academic Journal
- DOI
10.1034/j.1600-065x.2000.17809.x