Blocking Development of B Cells

Science's STKE  07 Dec 1999:
Vol. 1999, Issue 11, pp. tw6
DOI: 10.1126/stke.1999.11.tw6

Not all of the causes of genetic immunodeficiencies have been worked out. In cases in which B cells are lacking in the periphery, the Btk protein kinase signaling pathway is suspect, as it has turned out to be critical for B cell activation and development. Minegishi et al. have characterized the defect in a patient that had normal Btk. The mutation responsible in this case was the BLNK adaptor protein, which coordinates signaling from the B cell antigen receptor by binding to various kinases, lipases, and adaptors. Pappu et al. generated mice deficient in BLNK and report that these mice have the same defect--a block in the development of immature B cells from the pro-B to the pre-B stage that effectively prevents maturation of B cells and antibody production.

Pappu, R., Cheng, A.M., Li, B., Gong, Q., Chiu, C., Griffin, N., White, M., Sleckman, B.P., and Chan, A.C. (1999) Requirement for B cell linker protein (BLNK) in B cell development. Science 286: 1949-1954. [Abstract] [Full Text]

Minegishi, Y., Rohrer, J., Coustan-Smith, E., Lederman, H.M., Pappu, R., Campana, D., Chan, A.C., and Conley, M.E. (1999) An essential role for BLNK in human B cell development. Science 286: 1954-1957. [Abstract] [Full Text]