International Immunology, Vol. 11, No. 3, 453-460,
March 1999
© 1999 Japanese Society for Immunology
Partial block in B lymphocyte development at the transition into the pre-B cell receptor stage in Vpre-B1-deficient mice
Immunology Unit, Department of Cell and Molecular Biology, University of Lund, Box 7031, 220 07 Lund, Sweden
1 Department of Pathology and the Committee on Immunology, University of Chicago, IL 60637, USA
2 Basel Institute for Immunology, Basel, Switzerland
Correspondence to: I.-L. Mårtensson, The Babraham Institute, Cambridge CB2 4AT, UK
The surrogate light chain (SL) is composed of two polypeptides, Vpre-B and 
5. In large pre-BII cells the SL chain associates with Ig µ heavy chain (µH) to form the pre-B cell receptor (pre-BCR). In mice there are two Vpre-B genes which are 98% identical within the coding regions. The two genes are co-expressed at the RNA level and encode functional proteins that can assemble with 5. However, it is not known whether both gene products serve the same function in vivo. Here we have established mice that lack the Vpre-B1 gene (VpreB1–/–), but still express the Vpre-B2 gene, both as RNA and protein. In Vpre-B1–/– mice, the bone marrow cellularity and the percentage of B220+ cells is normal. However, among the B220+ cells, the percentage of pre-BI cells is increased, and the percentage of pre-BII and immature B cells is slightly decreased, suggesting that the lack of Vpre-B1 causes a partial block at the transition from pre-BI to pre-BII cells, i.e. into the pre-BCR stage. The number of cells that produce a functional pre-BCR is thus lower, but the cells that reach this stage are normal as they can be expanded by proliferation and then differentiate into more mature cells. The spleens of Vpre-B1 homozygous mutant mice show normal numbers of B and T lymphocytes. Moreover, the Ig loci are allelicly excluded and the homozygous mutant mice respond with normal levels of antigen-specific antibodies to T-dependent antigens. These results demonstrate that Vpre-B2 alone is capable of supporting B lymphocyte development in the bone marrow and can give rise to immuno-competent cells in the periphery.
Keywords: deficiency, 5, pre-B cell receptor, surrogate light chain, Vpre-B
Transmitting editor: A. Radbruch
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