Antigen-binding mutants of mouse myeloma cells.

Cook, Wayne D.; Scharff, Matthew D.

doi:10.1073/pnas.74.12.5687

Cited by 77 publications

(28 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Revertants in most cases were rare (<10-4 per cell), and this result contrasts with the findings of Cook and Scharff (10) (45). Nevertheless, this T15+ determinant appears to be distinct from the PC-binding site in the sense that its binding to the anti-T15+ reagent is not inhibited by PC.…”

contrasting

confidence: 56%

“…Culture fluid from 254 wells (46), fetal liver cell hybridomas (5), and as myeloma mutants (36,48). The characteristics of these various cell lines suggest that the presence of a light chain might (10) and is 10-fold higher than that observed earlier with a similar selection and screening on a hybridoma line secreting IgM specific for the hapten trinitrophenyl (30). Deletion mutations were isolated in both the PC and trinitrophenyl systems and seemed to be 10-fold more frequent here than in the earlier study.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Mutations affecting the structure and function of immunoglobulin M.

Shulman¹,

Heusser²,

Filkin³

et al. 1982

Mol. Cell. Biol.

View full text Add to dashboard Cite

Using a hybridoma cell line which secretes hapten-specific immunoglobulin M (IgM), we have isolated a variety of mutants which produce abnormal immunoglobulin. Immunoglobulin was tested for the size and composition of the component heavy and light chains and for variable and constant region related functional and serological activities. Some mutants secrete IgM which seems to be defective in hapten binding; others make IgM which appears not to activate complement. Many of the mutants secrete monomeric as opposed to pentameric IgM. In some cases, the defect apparently correlates with structural alterations in the mu heavy chain: partial deletion, polypeptide addition, and abnormal glycosylation have been observed. These mutant cell lines provide a means of identifying the structural basis of IgM function and of studying the biochemistry of IgM synthesis and processing.

show abstract

contrasting

confidence: 56%

mentioning

confidence: 99%

Mutations affecting the structure and function of immunoglobulin M.

Shulman¹,

Heusser²,

Filkin³

et al. 1982

Mol. Cell. Biol.

View full text Add to dashboard Cite

show abstract

“…In support of this notion is the finding that patients with systemic autoimmune diseases have increased levels of polyreactive B cells (22,23). In addition, examples exist in which NAA obtain increased autoreactivity via V gene mutation and isotype switching (24)(25)(26). In contrast, recent evidence has pointed to a role of natural IgM in maintaining selftolerance.…”

mentioning

confidence: 54%

Expression of Natural Autoantibodies in MRL-lpr Mice Protects from Lupus Nephritis and Improves Survival

Mannoor

Matejuk

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

Natural autoantibodies (NAA) and their associated B cells constitute a substantial proportion of the normal Ab and B cell repertoire. They often have weak reactivity toward a variety of self-Ags such as DNA, nucleoproteins, and phospholipids. It remains controversial whether NAA contribute to or protect from autoimmune diseases. Using site-directed transgenic (sd-tg) mice expressing a prototypic NAA, we investigated the effect of NAA and NAA-producing B cells in disease development in the autoimmune-prone MRL/MpJ-Faslpr (MRL-lpr) mice. We found that the expression of NAA in MRL-lpr mice prevented proteinuria and reduced kidney immune complex formation. The mice had significantly improved survival. Administration of the IgM NAA to MRL-lpr mice also delayed the onset of nephritis. The sd-tg MRL-lpr mice had decreased levels of anti-dsDNA Abs, anti-Hep2 nuclear Abs, and anti-Sm/ribonucleoprotein Abs. There is a shift in the IgG subclass profile from IgG2a and IgG3 to IgG1 in the sd-tg MRL-lpr mice. The CD4+ T cells from the sd-tg MRL-lpr mice had increased expression of the negative costimulatory molecule CTLA-4 and increased production of IL-10 as compared with those from the wild-type mice. Furthermore, the NAA B cells produced large amounts of IL-10 upon TLR stimulation. These results indicate that NAA and NAA-producing B cells play an important role in protection from lupus nephritis and suggest that the NAA B cells may have an immune regulatory function via the provision of IL-10.

show abstract

“…Identification of antigen-binding mutants. Cells are cloned in soft agar and overlaid with antigen as described in (34). The clone on the right is surrounded by an antigenantibody precipitate.…”

Section: Role Of Somatic Mutation In Antibody Diversitymentioning

confidence: 99%

Monoclonal Antibodies Reveal the Structural Basis of Antibody Diversity

Teillaud

Desaymard

Giusti

et al. 1983

Science

View full text Add to dashboard Cite

Hybridoma technology has made it possible to introduce into continuous culture normal antibody-forming cells and to obtain large amounts of the immunoglobulin produced by each of these cells. Examination of the structure of a number of monoclonal antibodies that react with a single antigen has provided new information on the structural basis of the specificity and affinity of antibodies. Comparisons of families of monoclonal antibodies derived from a single germ line gene revealed the importance of somatic mutation in generating antibody diversity. Monoclonal antibodies that react with variable regions of other monoclonals allow the further dissection and modulation of the immune response. Finally, the continued somatic instability of immunoglobulin genes in cultured antibody-forming cells makes it possible to determine the rate of somatic mutation and to generate mutant monoclonal antibodies that may be more effective serological reagents.

show abstract

Antigen-binding mutants of mouse myeloma cells.

Cited by 77 publications

References 31 publications

Mutations affecting the structure and function of immunoglobulin M.

Mutations affecting the structure and function of immunoglobulin M.

Expression of Natural Autoantibodies in MRL-lpr Mice Protects from Lupus Nephritis and Improves Survival

Monoclonal Antibodies Reveal the Structural Basis of Antibody Diversity

Contact Info

Product

Resources

About