| 1. |
- Källberg, Eva, et al.
(author)
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Somatic mutation of immunoglobulin V genes in vitro
- 1996
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In: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 271:5253, s. 9-1285
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Journal article (peer-reviewed)abstract
- The molecular mechanism behind affinity maturation is the introduction of point mutations in immunoglobulin (Ig) V genes, followed by the selective proliferation of B cells expressing mutants with increased affinity for antigen. An in vitro culture system was developed in which somatic hypermutation of Ig V genes was sustained in primed B cells. Cognate T cell help and cross-linking of the surface Ig were required, whereas the addition of lipopolysaccharide or a CD40 ligand to drive proliferation was insufficient. This system should facilitate understanding of the molecular and cellular mechanisms that regulate somatic mutation and B cell selection.
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| 2. |
- Källberg, Eva, et al.
(author)
-
The effect of carrier and carrier priming on the kinetics and pattern of somatic mutation in the V chi Ox1 gene
- 1995
-
In: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 25:8, s. 54-2349
-
Journal article (peer-reviewed)abstract
- Priming mice with a chicken gamma globulin (CGG) carrier protein significantly accelerated the onset of somatic mutation in the V chi Ox1 gene when the mice were subsequently immunized with 2-phenyl-5-oxazolone (phOx) coupled to CGG. The first mutations were already detected 7 days after immunization, while in the true primary response, they are not apparent until day 10. It was also found that comparing the mutation pattern of V chi Ox1 genes from hybridomas derived after immunization with phOx coupled to different carriers revealed quite distinct patterns of somatic mutation. Analysis of hybridoma sequences from the primary immune response to phOx-ovalbumin showed that the codons for Ser29, Ser31 and Lys45 were hot-spots for somatic mutation. Thus, the frequency and pattern of somatic mutations in the V chi Ox1 gene depends on the available T cell help as well as on the complex structure of the immunizing antigen.
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