VPREB1 explained

Immunoglobulin iota chain is a protein that in humans is encoded by the VPREB1 gene.^{[1] [2]} VPREB1 has also recently been designated CD179A (cluster of differentiation 179A).

Function

CD179a (VpreB) is a 126 aa-long polypeptide with apparent MW of 16-18 kDa. It is expressed selectively at the early stages of B cell development, namely, in proB and early preB cells. CD179a has an Ig V domain-like structure, but lacks the last beta-strand (beta7) of a typical V domain. Instead, it has a carboxyl terminal end that shows no sequence homologies to any other proteins. CD179a associates non-covalently with CD179b (lambda5 or lambda-like) carrying an Ig C domain-like structure to form an Ig light chain-like structure, which is called the surrogate light chain or pseudo light chain. In this complex, the incomplete V domain of CD179a appears to be complemented by the extra beta7 strand of CD179b. On the surface of early preB cells, CD179a/CD179b surrogate light chain is disulfide-linked to membrane-bound Ig mu heavy chain in association with a signal transducer CD79a/CD79b heterodimer to form a B cell receptor-like structure, so-called preB cell receptor (preBCR). Though no CD179a-related human disease or pathology has been reported yet, the deficiency of other components of preB cell receptor such as CD179b, Ig mu heavy chain and CD79a has been shown to result in severe impairment of B cell development and agammaglobulinemia in human. PreBCR transduces signals for: 1) cellular proliferation, differentiation from the proB cell to preB cell stage, 2) allelic exclusion at the Ig heavy chain gene locus, and 3) promotion of Ig light chain gene rearrangements. Thus, preBCR functions as a checkpoint in early B cell development to monitor the production of Ig mu heavy chain through a functional rearrangement of Ig heavy chain gene as well as the potency of Ig mu heavy chain to associate with Ig light chain.

Further reading

• Tsubata T, Reth M . The products of pre-B cell-specific genes (lambda 5 and VpreB) and the immunoglobulin mu chain form a complex that is transported onto the cell surface . The Journal of Experimental Medicine . 172 . 3 . 973–6 . September 1990 . 2117639 . 2188549 . 10.1084/jem.172.3.973 .
• Bauer SR, Kudo A, Melchers F . Structure and pre-B lymphocyte restricted expression of the VpreB in humans and conservation of its structure in other mammalian species . The EMBO Journal . 7 . 1 . 111–6 . January 1988 . 10.1002/j.1460-2075.1988.tb02789.x . 3258819 . 454222 .
• Guelpa-Fonlupt V, Bossy D, Alzari P, Fumoux F, Fougereau M, Schiff C . The human pre-B cell receptor: structural constraints for a tentative model of the pseudo-light (psi L) chain . Molecular Immunology . 31 . 14 . 1099–108 . October 1994 . 7935499 . 10.1016/0161-5890(94)90105-8 .
• Ohnishi K, Takemori T . Molecular components and assembly of mu.surrogate light chain complexes in pre-B cell lines . The Journal of Biological Chemistry . 269 . 45 . 28347–53 . November 1994 . 10.1016/S0021-9258(18)46934-7 . 7961773 . free .
• Guelpa-Fonlupt V, Tonnelle C, Blaise D, Fougereau M, Fumoux F . Discrete early pro-B and pre-B stages in normal human bone marrow as defined by surface pseudo-light chain expression . European Journal of Immunology . 24 . 1 . 257–64 . January 1994 . 8020565 . 10.1002/eji.1830240140 . 20176205 .
• Bornemann KD, Brewer JW, Perez E, Doerre S, Sita R, Corley RB . Secretion of soluble pre-B cell receptors by pre-B cells . Journal of Immunology . 158 . 6 . 2551–7 . March 1997 . 10.4049/jimmunol.158.6.2551 . 9058786 . 45625474 . free .
• Kawasaki K, Minoshima S, Nakato E, Shibuya K, Shintani A, Schmeits JL, Wang J, Shimizu N . One-megabase sequence analysis of the human immunoglobulin lambda gene locus . Genome Research . 7 . 3 . 250–61 . March 1997 . 9074928 . 10.1101/gr.7.3.250 . free .
• Fang T, Smith BP, Roman CA . Conventional and surrogate light chains differentially regulate Ig mu and Dmu heavy chain maturation and surface expression . Journal of Immunology . 167 . 7 . 3846–57 . October 2001 . 11564802 . 10.4049/jimmunol.167.7.3846 . free .
• Gisler R, Sigvardsson M . The human V-preB promoter is a target for coordinated activation by early B cell factor and E47 . Journal of Immunology . 168 . 10 . 5130–8 . May 2002 . 11994467 . 10.4049/jimmunol.168.10.5130 . free .
• Gauthier L, Rossi B, Roux F, Termine E, Schiff C . Galectin-1 is a stromal cell ligand of the pre-B cell receptor (BCR) implicated in synapse formation between pre-B and stromal cells and in pre-BCR triggering . Proceedings of the National Academy of Sciences of the United States of America . 99 . 20 . 13014–9 . October 2002 . 12271131 . 130578 . 10.1073/pnas.202323999 . 2002PNAS...9913014G . free .
• Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I . A genome annotation-driven approach to cloning the human ORFeome . Genome Biology . 5 . 10 . R84 . 2005 . 15461802 . 545604 . 10.1186/gb-2004-5-10-r84 . free .
• Rossi B, Espeli M, Schiff C, Gauthier L . Clustering of pre-B cell integrins induces galectin-1-dependent pre-B cell receptor relocalization and activation . Journal of Immunology . 177 . 2 . 796–803 . July 2006 . 16818733 . 10.4049/jimmunol.177.2.796 . free .

Notes and References

1. Bauer SR, Huebner K, Budarf M, Finan J, Erikson J, Emanuel BS, Nowell PC, Croce CM, Melchers F . The human Vpre B gene is located on chromosome 22 near a cluster of V lambda gene segments . Immunogenetics . 28 . 5 . 328–33 . Nov 1988 . 3139558 . 10.1007/BF00364231 . 6981867 .
2. Web site: Entrez Gene: VPREB1 pre-B lymphocyte gene 1.