kappa gene diversity among the clonal progeny of pre-B lymphocytes.

Campbell

The Journal of Experimental Medicine

1989

We have previously isolated Ig variants (6) of 38C13, a carcinogen-induced murine B cell lymphoma (7) . These variants arose in tumor-bearing animals that were treated with antiidiotypic mAbs . Although a high percentage of the animals were cured, some developed tumors despite the therapy. Analysis of the variant cells revealed that they expressed sIg but failed to react with the antiidiotypic antibody. mAbs were produced that could discriminate between the Ig produced by the parental tumor and by each of the variants . Further analysis showed that the Ig protein expressed by the variants contained identical heavy chains but differed in their light chains . Southern blot analysis showed identical rearrangements at the H chain locus and established that the variants were clonally related . However, the variants differed from each other in their L chain gene rearrangement patterns .The Ig V region genes expressed by these variants were cloned and sequenced .As expected, the V H genes were identical in all variants and in the parental 38C13

Section: Discussionmentioning

confidence: 68%

Functional immunoglobulin light chain genes are replaced by ongoing rearrangements of germline V kappa genes to downstream J kappa segment in a murine B cell line.

Campbell

The Journal of Experimental Medicine

1989

The molecular evolution of the immune response: idiotope‐specific suppression indicates that B cells express germ‐line‐encoded V genes prior to antigenic stimulation

Manser

Gefter

1986

Eur J Immunol

Antibodies expressed by the immune B cell population are characterized by variable region amino acid substitutions resulting from somatic nucleotide replacement (somatic mutation). This is not true of antibodies expressed by the "naive" B cell population. It is at present unclear whether this discrepancy is due to the preferential clonal selection of a pre-existing subpopulation of naive B cells that express variable regions altered via nucleotide replacement, or whether the process of nucleotide replacement occurs only during the antigen-dependent stages of B cell differentiation. To address this question we have used anti-idiotypic suppression to functionally delete B cells that express particular variable-region structures from the antigen-responsive repertoire. Suppression of the major cross-reactive idiotype (IdCR) expressed in strain A mice in response to p-azophenylarsonate (Ars) was induced using the monoclonal anti-IdCR antibody AD8. The idiotope recognized by AD8 is easily destroyed by alteration of IdCR variable-region structure via nucleotide replacement. The IdCR anti-Ars immune repertoire is characterized by antibodies that lack the AD8-cognate idiotope due to nucleotide replacement. However, complete suppression of the IdCR could reproducibly be achieved by administration of AD8 prior to Ars immunization. This result indicates that all IdCR-expressing B cells also express the AD8-cognate idiotope prior to immunization. Thus, somatic nucleotide replacement must occur exclusively during the antigen-dependent stages of B cell differentiation in this system.

A temperature-sensitive mutant of Abelson murine leukemia virus confers inducibility of IgM expression to transformed lymphoid cells.

Takemori¹,

Miyazoe²,

Shirasawa³

et al. 1987

The EMBO Journal

Lymphoid cell lines were isolated that were inducible for the expression of surface immunoglobulin by shift from 35.5 to 39.5 degrees C after infection of mouse bone marrow cells with a mutagen‐treated Abelson murine leukemia virus. Virus produced by one of the cell lines (ts49) transmitted the temperature‐sensitive phenotype to new lymphoid transformants as well as to NIH/3T3 cells. In addition, the tyrosine autophosphorylating activity of the p120gag‐abl protein synthesized in ts49‐transformed cells was found to be temperature‐sensitive. Shift experiments using ts49‐transformed lymphoid cells showed that at 39.5 degrees C they synthesize increased amounts of mu and kappa chain RNA and protein, and that they can be further induced to secrete IgM when treated with lipopolysaccharide.