Isolation of variants of mouse myeloma X63 that express changed immunoglobulin class.

Radbruch, Andreas; Liesegang, Bernhard; Rajewsky, Klaus

doi:10.1073/pnas.77.5.2909

Cited by 93 publications

(50 citation statements)

References 19 publications

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“…In accordance with this scenario, Ͻ30% of C␥1-cre B cells underwent Cre-mediated recombination in spontaneous GCs of gut-associated lymphoid tissues where TGF-␤ represents the predominant cytokine, promoting switching to IgA (29). Cre-mediated recombination in C␥1-cre B cells switching to isotypes other than IgG1 may also result from CSR involving different C H genes on the two IgH chromosomes (30) or sequential switching from C␥1 to distal C H isotypes (31), except in the case of cells expressing IgG3. The latter mechanism may contribute to the generation of IgA ϩ B cells because the predominant IgH allotype expressed by IgG1 ϩ B cells in C␥1-cre mice was specifically overrepresented within the fraction of IgA ϩ cells that had undergone Cre-mediated recombination (data not shown).…”

Section: Transcription At Multiple Ch Loci Precedes Csr In Individualmentioning

confidence: 91%

Tracking germinal center B cells expressing germ-line immunoglobulin γ1 transcripts by conditional gene targeting

Casola

Cattoretti

Uyttersprot

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

211

266

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Germinal centers (GCs) represent the main sites for the generation of high-affinity, class-switched antibodies during T cell-dependent antibody responses. To study gene function specifically in GC B cells, we generated Cγ1-cre mice in which the expression of Cre recombinase is induced by transcription of the Ig γ1 constant region gene segment (Cγ1). In these mice, Cre-mediated recombination at the fas , Ig β, IgH , and Rosa26 loci occurred in GC B cells as early as 4 days after immunization with T cell-dependent antigens and involved >85% of GC B cells at the peak of the GC reaction. Less than 2% of IgM + B cells showed Cre-mediated recombination. These cells carried few Ig somatic mutations, expressed germ-line Cγ1- and activation-induced cytidine deaminase-specific transcripts and likely include GC B cell founders and/or plasma cell precursors. Cre-mediated recombination involved most IgG1, but also a fraction of IgG3-, IgG2a-, IgG2b-, and IgA-expressing GC and post-GC B cells. This result indicates that a GC B cell can transcribe more than one downstream C H gene before undergoing class switch recombination. The efficient induction of Cre expression in GC B cells makes the Cγ1-cre allele a powerful tool for the genetic analysis of these cells, as well as, in combination with a suitable marker for Cre-mediated recombination, the tracking of class-switched memory B and plasma cells in vivo . To expedite the genetic analysis of GC B cells, we have established Cγ1-cre F 1 embryonic stem cells, allowing further rounds of gene targeting and the cloning of compound mutants by tetraploid embryo complementation.

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Section: Transcription At Multiple Ch Loci Precedes Csr In Individualmentioning

confidence: 91%

Tracking germinal center B cells expressing germ-line immunoglobulin γ1 transcripts by conditional gene targeting

Casola

Cattoretti

Uyttersprot

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

211

266

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“…Spontaneous CSR has also been found in transformed B cell lines (42,43). In resting human B cells, a significant level of ␥1, ␥3, and H chain GLTs are found, but in the absence of stimulatory signals no CSR was observed (44).…”

Section: Discussionmentioning

confidence: 97%

Spontaneous Class Switch Recombination in B Cell Lymphopoiesis Generates Aberrant Switch Junctions and Is Increased after VDJ Rearrangement

Edry

Koralov

Rajewsky

et al. 2007

The Journal of Immunology

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Mature B cells replace the μ constant region of the H chain with a downstream isotype in a process of class switch recombination (CSR). Studies suggest that CSR induction is limited to activated mature B cells in the periphery. Recently, we have shown that CSR spontaneously occur in B lymphopoiesis. However, the mechanism and regulation of it have not been defined. In this study, we show that spontaneous CSR occurs at all stages of B cell development and generates aberrant joining of the switch junctions as revealed by: 1) increased load of somatic mutations around the CSR break points, 2) reduced sequence overlaps at the junctions, and 3) excessive switch region deletion. In addition, we found that incidence of spontaneous CSR is increased in cells carrying VDJ rearrangements. Our results reveal major differences between spontaneous CSR in developing B cells and CSR induced in mature B cells upon activation. These differences can be explained by deregulated expression or function of activation-induced cytidine deaminase early in B cell development.

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“…We feel that the class switch-related events that we have observed do not represent the low-frequency, homologous recombination-mediated events observed in myelomas (17,33) for multiple reasons, including the following. (i) The frequency of switching in these A-MuLV transformants is very high in some isolates (5,11).…”

Section: Resultsmentioning

confidence: 99%

“…(ii) The class switch events occurred between the S region sequences, regions previously demonstrated to be involved in physiological class switch events. (iii) Like 18-8, all of the pre-B lines studied thus far have a predisposition to switch from p. to Y2b (see below), and yet the S, and Sy2b regions are the most divergent S region sequences; low-frequency class switch variants of myelomas usually occur between (closely related) subclasses (17,33). (iv) line and other activity during propagation (5; K. Kruger and F. W. Alt, unpublished data).…”

Section: Resultsmentioning

confidence: 99%

Molecular basis of heavy-chain class switching and switch region deletion in an Abelson virus-transformed cell line.

DePinho¹,

Kruger²,

Andrews³

et al. 1984

Mol. Cell. Biol.

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We demonstrated that a subclone of an Abelson murine leukemia virus-transformed B-lymphoid cell line switched from I. to '2b expression in vitro, by the classical recombination-deletion mechanism. In this line, the expressed VHDJH region and the Cy2b constant region gene were juxtaposed by a recombination event which linked the highly repetitive portions of the S,, and Sy2b regions and resulted in the loss of the C, gene from the intervening region. An additional recombination event in this subclone involved an internal deletion in the S,J region of the expressed (switched) allele. One end of this deletion occurred very close to the switch recombination point. Despite the recombination-deletion mechanism of switching, the y2b-producing line retained two copies of the C, gene and two copies of the sequence just 5' to the Sy2b recombination point. The possible significance of the retention of these sequences to the mechanism of class switching is discussed.

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Isolation of variants of mouse myeloma X63 that express changed immunoglobulin class.

Cited by 93 publications

References 19 publications

Tracking germinal center B cells expressing germ-line immunoglobulin γ1 transcripts by conditional gene targeting

Tracking germinal center B cells expressing germ-line immunoglobulin γ1 transcripts by conditional gene targeting

Spontaneous Class Switch Recombination in B Cell Lymphopoiesis Generates Aberrant Switch Junctions and Is Increased after VDJ Rearrangement

Molecular basis of heavy-chain class switching and switch region deletion in an Abelson virus-transformed cell line.

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