Abstract
We describe here two alleles, an allele of the lambda1 locus present in the SJL strain (rlambda1lo) and an allele of the lambda1 locus present in the BALB/c strain (rlambda1 +), of a regulatory gene locus which specifically influences the expression of the mouse lambda1 light chain structural gene. The rlambda1 regulatory gene is not linked to either the major histocompatibility complex or to the heavy-chain allogroup but appears to be linked to the lambda1 structural gene locus. In the homozygous state, the present of the rlambda1lo allele results in a 50- fold reduction in the number of lambda1 antigen-sensitive, bone-marrow derived lymphocytes (ASCs) compared to the presence of the rlambda1 + allele. However, those few lambda1ASCs present in rlambda1lo homozygotes can be induced normally to produce lambda1 light chains indistinguishable from those found in rlambda1 + homozygotes. The reduction in lambda1ASC's due to the rlambda1lo allele results both in a reduction in the amount of lambda1 Ig in the serum and also in a large variation in the magnitude of the lambda1 antibody response to alpha(1,3) dextran by individual animals. This variation permits the estimate that, on the average, 50 B cells of anti-alpha(1,3) specificity must be present per animal to permit a measurable response. Surprisingly, the expression of a gene locus regulating lambda1 light chain expression (rlambda1 locus) shows a clear gene dosage effect with rlambda1lo/rlambda1 + heterozygotes having 1/2 the number of lambda1ASCs and 1/2 the amount of serum lambda1 Ig as rlambda1 +/rlambda1 + homozygotes. This fact permits an analysis of the relationship between germ-line v-genes and their individual expression in serum Ig. The rlambda1 locus controls specifically a DNA-level event which occurs in stem cells as they become committed to lambda1 light chain expression. We postulate that the rlambda1 locus represents one of the DNA level recognition sites involved in the translocation event which places the vlambda1 and clambda1 structural genes in a transcriptional unit.
Full Text
The Full Text of this article is available as a PDF (944.5 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Blaser K., Eisen H. N. Lambda2 light chains in normal mouse immunoglobulins. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1495–1499. doi: 10.1073/pnas.75.3.1495. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blomberg B., Geckeler W. R., Weigert M. Genetics of the antibody response to dextran in mice. Science. 1972 Jul 14;177(4044):178–180. doi: 10.1126/science.177.4044.178. [DOI] [PubMed] [Google Scholar]
- Brack C., Tonegawa S. Variable and constant parts of the immunoglobulin light chain gene of a mouse myeloma cell are 1250 nontranslated bases apart. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5652–5656. doi: 10.1073/pnas.74.12.5652. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carson D., Weigert M. Immunochemical analysis of the cross-reacting idiotypes of mouse myeloma proteins with anti-dextran activity and normal anti-dextran antibody. Proc Natl Acad Sci U S A. 1973 Jan;70(1):235–239. doi: 10.1073/pnas.70.1.235. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Coffman R. L., Cohn M. The class of surface immunoglobulin on virgin and memory B lymphocytes. J Immunol. 1977 May;118(5):1806–1815. [PubMed] [Google Scholar]
- Dubiski S. Suppression of synthesis of allotypically defined immunoglobulins and compensation by another sub-class of immunoglobulin. Nature. 1967 Jun 24;214(5095):1365–1366. doi: 10.1038/2141365a0. [DOI] [PubMed] [Google Scholar]
- Gilmore-Hebert M., Wall R. Immunoglobulin light chain mRNA is processed from large nuclear RNA. Proc Natl Acad Sci U S A. 1978 Jan;75(1):342–345. doi: 10.1073/pnas.75.1.342. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jacobson E. B., Herzenberg L. A. Active suppression of immunoglobulin allotype synthesis. I. Chronic suppression after perinatal exposure to maternal antibody to paternal allotype in (SJL x BALB-c)F 1 mice. J Exp Med. 1972 May 1;135(5):1151–1162. doi: 10.1084/jem.135.5.1151. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kelus A. S., Weiss S. Variant strain of rabbits lacking immunoglobulin kappa polypeptide chain. Nature. 1977 Jan 13;265(5590):156–158. doi: 10.1038/265156a0. [DOI] [PubMed] [Google Scholar]
- Milstein C., Brownlee G. G., Cartwright E. M., Jarvis J. M., Proudfoot N. J. Sequence analysis of immunoglobulin light chain messenger RNA. Nature. 1974 Nov 29;252(5482):354–359. doi: 10.1038/252354a0. [DOI] [PubMed] [Google Scholar]
- Mäkelä O., Cross A. M. The diversity and specialization of immunocytes. Prog Allergy. 1970;14:145–207. doi: 10.1159/000289379. [DOI] [PubMed] [Google Scholar]
- Schechter I., Burstein Y. Identification of N-terminal methionine in the precursor of immunoglobulin light chain. Initiation of translation of messenger ribonucleic acid in plants and animals. Biochem J. 1976 Mar 1;153(3):543–550. doi: 10.1042/bj1530543. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Staats J. Standardized nomenclature for inbred strains of mice: sixth listing. Cancer Res. 1976 Dec;36(12):4333–4377. [PubMed] [Google Scholar]
- Tonegawa S., Hozumi N., Matthyssens G., Schuller R. Somatic changes in the content and context of immunoglobulin genes. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 2):877–889. doi: 10.1101/sqb.1977.041.01.097. [DOI] [PubMed] [Google Scholar]
- Tonegawa S., Maxam A. M., Tizard R., Bernard O., Gilbert W. Sequence of a mouse germ-line gene for a variable region of an immunoglobulin light chain. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1485–1489. doi: 10.1073/pnas.75.3.1485. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walzer P. D., Kunkel H. G. The correlation of serum IgD concentration with Gm allotype. J Immunol. 1974 Jul;113(1):274–278. [PubMed] [Google Scholar]
- Weigert M., Riblet R. Genetic control of antibody variable regions. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 2):837–846. doi: 10.1101/sqb.1977.041.01.093. [DOI] [PubMed] [Google Scholar]
- Wuilmart C., Urbain J., Givol D. On the location of palindromes in immunoglobulin genes. Proc Natl Acad Sci U S A. 1977 Jun;74(6):2526–2530. doi: 10.1073/pnas.74.6.2526. [DOI] [PMC free article] [PubMed] [Google Scholar]