Double Isotype Production by a Neoplastic B Cell Line. II. Allelically Excluded Production of Mu and Gamma 1 Heavy Chains Without CH Gene Rearrangement

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1986 Aug 1

PMID 3088208

Citations 19

Authors

Y W Chen

C Word

V Dev

J W UHR

E S Vitetta

P W Tucker

Affiliations

Soon will be listed here.

Abstract

In our accompanying paper, we described a switch variant (BCL1.2.58) that expresses membrane and secreted forms of IgM and IgG1. Both IgM and IgG1 share the same idiotype and use the same VDJ rearrangement. Here, a detailed Southern blot analysis of the entire constant region of the Ig heavy chain (Ig CH) locus of parental (BCL1.B1) and variants (BCL1.B2) DNA showed no detectable rearrangement. Similar analysis of the JH-C mu region led to the conclusion that two heavy chain alleles present in the IgM/IgG1-producing variants carried the same VDJ rearrangement but differed in their 3' flanking regions. One chromosome 12 did not carry any Ig CH genes, whereas, the other chromosome 12 carried one copy of CH genes. In BCL1.B1, however, each of the chromosome 12 alleles carried a full copy of CH genes. Karyotypic analysis confirmed the presence of two translocated t(12;16) chromosomes in both BCL1.2.58 and BCL1.B1 cells, with a break 5' to the VH locus at the distal region (12F2) of chromosome 12, and at the proximal region below the centromere (16B3) of chromosome 16. We conclude that double production of IgM and IgG1 in BCL1.B2 is accomplished by transcription of the corresponding CH genes in germline configuration using a single VDJ on the same chromosome 12.

Citing Articles

Enhancement of antibody class-switch recombination by the cumulative activity of four separate elements.

Dunnick W, Shi J, Zerbato J, Fontaine C, Collins J J Immunol. 2011; 187(9):4733-43.

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The role of germline promoters and I exons in cytokine-induced gene-specific class switch recombination.

Dunnick W, Shi J, Holden V, Fontaine C, Collins J J Immunol. 2010; 186(1):350-8.

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Trans-chromosomal recombination within the Ig heavy chain switch region in B lymphocytes.

Kingzette M, Yam P, Zhai S, Knight K Proc Natl Acad Sci U S A. 1998; 95(20):11840-5.

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Molecular characterization of IgA- and/or IgG-switched chronic lymphocytic leukemia B cells.

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Interleukin (IL)-4-independent immunoglobulin class switch to immunoglobulin (Ig)E in the mouse.

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References

SEABRIGHT M . A rapid banding technique for human chromosomes. Lancet. 1971; 2(7731):971-2. DOI: 10.1016/s0140-6736(71)90287-x. View

Yuan D, Gilliam A, Tucker P . Regulation of expression of immunoglobulins M and D in murine B cells. Fed Proc. 1985; 44(10):2652-9. View

Kearney J, Cooper M, Lawton A . B cell differentiation induced by lipopolysaccharide. IV. Development of immunoglobulin class restriction in precursors of IgG-synthesizing cells. J Immunol. 1976; 117(5 Pt 1):1567-72. View

Rigby P, Dieckmann M, Rhodes C, Berg P . Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977; 113(1):237-51. DOI: 10.1016/0022-2836(77)90052-3. View

Pernis B, Forni L, Luzzati A . Synthesis of multiple immunoglobulin classes by single lymphocytes. Cold Spring Harb Symp Quant Biol. 1977; 41 Pt 1:175-83. DOI: 10.1101/sqb.1977.041.01.023. View

Vitetta E, Assisi F, Strober S . The relationship between surface immunoglobulin isotype and immune function of murine B lymphocytes. III. Expression of a single predominant isotype on primed and unprimed B cells. J Exp Med. 1978; 147(5):1374-94. PMC: 2184263. DOI: 10.1084/jem.147.5.1374. View

Honjo T, Kataoka T . Organization of immunoglobulin heavy chain genes and allelic deletion model. Proc Natl Acad Sci U S A. 1978; 75(5):2140-4. PMC: 392507. DOI: 10.1073/pnas.75.5.2140. View

Marcu K, Schibler U, PERRY R . Nuclear transcripts of mouse heavy chain immunoglobulin genes contain only the expressed class of C-region sequences. Science. 1979; 204(4397):1087-8. DOI: 10.1126/science.109919. View

Honjo T, Obata M, Kataoka T, Kawakami T, Takahashi N, Mano Y . Cloning and complete nucleotide sequence of mouse immunoglobulin gamma 1 chain gene. Cell. 1979; 18(2):559-68. DOI: 10.1016/0092-8674(79)90072-2. View

10.

Tucker P, Marcu K, Slightom J, Blattner F . Structure of the constant and 3' untranslated regions of the murine gamma 2b heavy chain messenger RNA. Science. 1979; 206(4424):1299-303. DOI: 10.1126/science.117548. View

11.

Isakson P, UHR J, Krolick K, FINKELMAN F, Vitetta E . Acquisition of cell surface IgD after in vitro culture of neoplastic B cells from the murine tumor BCL1. J Exp Med. 1980; 151(3):749-54. PMC: 2185800. DOI: 10.1084/jem.151.3.749. View

12.

Chiorazzi N, Fu S, KUNKEL H . Stimulation of human B lymphocytes by antibodies to IgM and IgG: functional evidence for the expression of IgG on B-lymphocyte surface membranes. Clin Immunol Immunopathol. 1980; 15(3):301-13. DOI: 10.1016/0090-1229(80)90042-2. View

13.

Maxam A, Gilbert W . Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980; 65(1):499-560. DOI: 10.1016/s0076-6879(80)65059-9. View

14.

DEustachio P, Pravtcheva D, Marcu K, Ruddle F . Chromosomal location of the structural gene cluster encoding murine immunoglobulin heavy chains. J Exp Med. 1980; 151(6):1545-50. PMC: 2185885. DOI: 10.1084/jem.151.6.1545. View

15.

Newell N, Richards J, Tucker P, Blattner F . J genes for heavy chain immunoglobulins of mouse. Science. 1980; 209(4461):1128-32. DOI: 10.1126/science.6250219. View

16.

Gronowicz E, Doss C, Howard F, Morrison D, Strober S . An in vitro line of the B cell tumor BCL1 can be activated by LPS to secrete IgM1. J Immunol. 1980; 125(3):976-80. View

17.

Voss R, Maftzir G, Slavin S . Cytogenetic analysis of the spontaneous murine B-cell leukemia (BCL1). Leuk Res. 1980; 4(3):325-32. DOI: 10.1016/0145-2126(80)90040-5. View

18.

Liu C, Tucker P, MUSHINSKI J, Blattner F . Mapping of heavy chain genes for mouse immunoglobulins M and D. Science. 1980; 209(4463):1348-53. DOI: 10.1126/science.6774414. View

19.

Tucker P, Liu C, MUSHINSKI J, Blattner F . Mouse immunoglobulin D: messenger RNA and genomic DNA sequences. Science. 1980; 209(4463):1353-60. DOI: 10.1126/science.6968091. View

20.

MUSHINSKI J, Blattner F, Owens J, Finkelman F, Kessler S, Fitzmaurice L . Mouse immunoglobulin D: construction and characterization of a cloned delta chain cDNA. Proc Natl Acad Sci U S A. 1980; 77(12):7405-9. PMC: 350512. DOI: 10.1073/pnas.77.12.7405. View