Genes Required for B Cell Development

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2003 Dec 9

PMID 14660738

Citations 5

Authors

Mary Ellen Conley

Affiliations

Soon will be listed here.

Abstract

Mutations in a variety of genes can cause congenital agammaglobulinemia and a failure of B cell development. The currently known genes encode components of the pre-B cell receptor or proteins that are activated by cross-linking of the pre-B cell receptor. Defects in these genes result in a block in B cell differentiation at the pro-B to pre-B cell transition. A patient with a translocation involving a previously unknown gene, LRRC8, demonstrated a block at exactly the same point in B cell differentiation (see the related article beginning on page 1707). It will be interesting to determine whether the protein encoded by this gene interacts with the pre-B cell receptor signal transduction pathway or is involved in a new pathway.

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References

Hoffman H, Bastian J, Bird L . Humoral immunodeficiency with facial dysmorphology and limb anomalies: a new syndrome. Clin Dysmorphol. 2001; 10(1):1-8. DOI: 10.1097/00019605-200101000-00001. View

Minegishi Y, Coustan-Smith E, Rapalus L, Ersoy F, Campana D, Conley M . Mutations in Igalpha (CD79a) result in a complete block in B-cell development. J Clin Invest. 1999; 104(8):1115-21. PMC: 408581. DOI: 10.1172/JCI7696. View

Conley M, Rohrer J, Rapalus L, Boylin E, Minegishi Y . Defects in early B-cell development: comparing the consequences of abnormalities in pre-BCR signaling in the human and the mouse. Immunol Rev. 2001; 178:75-90. DOI: 10.1034/j.1600-065x.2000.17809.x. View

Srivannaboon K, Conley M, Coustan-Smith E, Wang W . Hypogammaglobulinemia and reduced numbers of B-cells in children with myelodysplastic syndrome. J Pediatr Hematol Oncol. 2001; 23(2):122-5. DOI: 10.1097/00043426-200102000-00011. View

Verloes A, Dresse M, Keutgen H, Asplund C, Smith C . Microphthalmia, facial anomalies, microcephaly, thumb and hallux hypoplasia, and agammaglobulinemia. Am J Med Genet. 2001; 101(3):209-12. DOI: 10.1002/ajmg.1373. View

Lopez Granados E, Porpiglia A, Hogan M, Matamoros N, Krasovec S, Pignata C . Clinical and molecular analysis of patients with defects in micro heavy chain gene. J Clin Invest. 2002; 110(7):1029-35. PMC: 151150. DOI: 10.1172/JCI15658. View

Conley M, Howard V . Clinical findings leading to the diagnosis of X-linked agammaglobulinemia. J Pediatr. 2002; 141(4):566-71. DOI: 10.1067/mpd.2002.127711. View

Hardy R . B-cell commitment: deciding on the players. Curr Opin Immunol. 2003; 15(2):158-65. DOI: 10.1016/s0952-7915(03)00012-8. View

Sawada A, Takihara Y, Kim J, Matsuda-Hashii Y, Tokimasa S, Fujisaki H . A congenital mutation of the novel gene LRRC8 causes agammaglobulinemia in humans. J Clin Invest. 2003; 112(11):1707-13. PMC: 281644. DOI: 10.1172/JCI18937. View

10.

Campana D, Farrant J, Inamdar N, Webster A, Janossy G . Phenotypic features and proliferative activity of B cell progenitors in X-linked agammaglobulinemia. J Immunol. 1990; 145(6):1675-80. View

11.

Vetrie D, Vorechovsky I, Sideras P, Holland J, Davies A, Flinter F . The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases. Nature. 1993; 361(6409):226-33. DOI: 10.1038/361226a0. View

12.

Tsukada S, Saffran D, Rawlings D, Parolini O, Allen R, Klisak I . Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia. Cell. 1993; 72(2):279-90. DOI: 10.1016/0092-8674(93)90667-f. View

13.

Smith C, Baskin B, Zhou J, Olsson P, Maniar H, Kjellen P . Expression of Bruton's agammaglobulinemia tyrosine kinase gene, BTK, is selectively down-regulated in T lymphocytes and plasma cells. J Immunol. 1994; 152(2):557-65. View

14.

Loffert D, Schaal S, Ehlich A, Hardy R, Zou Y, Muller W . Early B-cell development in the mouse: insights from mutations introduced by gene targeting. Immunol Rev. 1994; 137:135-53. DOI: 10.1111/j.1600-065x.1994.tb00662.x. View

15.

Minegishi Y, Rohrer J, Coustan-Smith E, Lederman H, Pappu R, Campana D . An essential role for BLNK in human B cell development. Science. 1999; 286(5446):1954-7. DOI: 10.1126/science.286.5446.1954. View

16.

Revy P, Busslinger M, Tashiro K, Arenzana F, Pillet P, Fischer A . A syndrome involving intrauterine growth retardation, microcephaly, cerebellar hypoplasia, B lymphocyte deficiency, and progressive pancytopenia. Pediatrics. 2000; 105(3):E39. DOI: 10.1542/peds.105.3.e39. View

17.

Nomura K, Kanegane H, Karasuyama H, Tsukada S, Agematsu K, Murakami G . Genetic defect in human X-linked agammaglobulinemia impedes a maturational evolution of pro-B cells into a later stage of pre-B cells in the B-cell differentiation pathway. Blood. 2000; 96(2):610-7. View

18.

Adderson E, Viskochil D, Carey J, Shigeoka A, Christenson J, Bohnsack J . Growth failure, intracranial calcifications, acquired pancytopenia, and unusual humoral immunodeficiency: a genetic syndrome?. Am J Med Genet. 2000; 95(1):17-20. DOI: 10.1002/1096-8628(20001106)95:1<17::aid-ajmg5>3.0.co;2-m. View

19.

Genevier H, Hinshelwood S, Gaspar H, Rigley K, Brown D, Saeland S . Expression of Bruton's tyrosine kinase protein within the B cell lineage. Eur J Immunol. 1994; 24(12):3100-5. DOI: 10.1002/eji.1830241228. View

20.

Rajewsky K . Clonal selection and learning in the antibody system. Nature. 1996; 381(6585):751-8. DOI: 10.1038/381751a0. View