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Editing anti-DNA B cells by Vlambdax.

Li Y, Louzoun Y, Weigert M - J. Exp. Med. (2004)

Bottom Line: However, the lambda locus, either of man or mouse, does not allow V gene replacement.We have found that in anti-DNA heavy chain transgenic mice (tgs) VH3H9/56R, B cells that express anti-DNA receptors comprised of lambda1 in association with an anti-DNA heavy chain often coexpress a kappa chain that prevents DNA binding.Here we describe a mechanism of preventing DNA binding by expression of a rarely used member of the Vlambda family, Vlambdax.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, Princeton University, NJ 08544, USA. yijinli@uchicago.edu

ABSTRACT
Receptor editing is performed by replacement of Vkappa genes that contribute to autoreactivity. In addition, the Ckappa locus can be deleted by Vkappa rearrangement to intronic or 3' of Ckappa RS sequences (also referred to as kappa deletion elements). B cells that delete the Ckappa can then express lambda light chains. However, the lambda locus, either of man or mouse, does not allow V gene replacement. Nor does it appear to be deleted. Therefore, editing of autoreactive lambda B cells may require alternative pathways. We have found that in anti-DNA heavy chain transgenic mice (tgs) VH3H9/56R, B cells that express anti-DNA receptors comprised of lambda1 in association with an anti-DNA heavy chain often coexpress a kappa chain that prevents DNA binding. We speculate that such isotypically included cells may have low anti-DNA receptor densities, a feature that may lead to self-tolerance. Here we describe a mechanism of preventing DNA binding by expression of a rarely used member of the Vlambda family, Vlambdax. The lambdax B cells of the tgs also express CD25 and may represent B cells that have exhausted light chain editing possibilities.

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Related in: MedlinePlus

CD25+/IgM+/IgD+ spleen B cells of VH3H9/56R mice. (A) Spleen cells from VH3H9/56R BALB/c mice and its nontransgenic littermate were stained with anti-B220 and CD25. Percentages of CD25+/B220+ cells in a lymphoid gate are indicated. (B) Spleen cells from VH3H9/56R BALB/c mice were stained with κ, λ, IgM, and IgD. Results of IgM/IgD and κ/λ staining are shown for the whole lymphocyte gate (left) and the B220+/ CD25+ gate (right).
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fig1: CD25+/IgM+/IgD+ spleen B cells of VH3H9/56R mice. (A) Spleen cells from VH3H9/56R BALB/c mice and its nontransgenic littermate were stained with anti-B220 and CD25. Percentages of CD25+/B220+ cells in a lymphoid gate are indicated. (B) Spleen cells from VH3H9/56R BALB/c mice were stained with κ, λ, IgM, and IgD. Results of IgM/IgD and κ/λ staining are shown for the whole lymphocyte gate (left) and the B220+/ CD25+ gate (right).

Mentions: In our studies on site-directed anti-DNA H chain tgs, we found that the VH3H9/56R BALB/c tg has an unusual set of spleen B cells that express the activation marker CD25. CD25 is the IL-2 receptor α chain and is reported to be expressed on both pre–B cells and activated B cells (28, 29). The CD25+ B cells represent 13.2% (SD 2.2, n = 7) of the B220+ B cell population of VH3H9/56R, but these B cells are not detectable in either the nontransgenic littermates of this tg (Fig. 1 A) or tgs with anti-DNA H chain transgenes such as 3H9 and 3H9/56R/76R (unpublished data).


Editing anti-DNA B cells by Vlambdax.

Li Y, Louzoun Y, Weigert M - J. Exp. Med. (2004)

CD25+/IgM+/IgD+ spleen B cells of VH3H9/56R mice. (A) Spleen cells from VH3H9/56R BALB/c mice and its nontransgenic littermate were stained with anti-B220 and CD25. Percentages of CD25+/B220+ cells in a lymphoid gate are indicated. (B) Spleen cells from VH3H9/56R BALB/c mice were stained with κ, λ, IgM, and IgD. Results of IgM/IgD and κ/λ staining are shown for the whole lymphocyte gate (left) and the B220+/ CD25+ gate (right).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211795&req=5

fig1: CD25+/IgM+/IgD+ spleen B cells of VH3H9/56R mice. (A) Spleen cells from VH3H9/56R BALB/c mice and its nontransgenic littermate were stained with anti-B220 and CD25. Percentages of CD25+/B220+ cells in a lymphoid gate are indicated. (B) Spleen cells from VH3H9/56R BALB/c mice were stained with κ, λ, IgM, and IgD. Results of IgM/IgD and κ/λ staining are shown for the whole lymphocyte gate (left) and the B220+/ CD25+ gate (right).
Mentions: In our studies on site-directed anti-DNA H chain tgs, we found that the VH3H9/56R BALB/c tg has an unusual set of spleen B cells that express the activation marker CD25. CD25 is the IL-2 receptor α chain and is reported to be expressed on both pre–B cells and activated B cells (28, 29). The CD25+ B cells represent 13.2% (SD 2.2, n = 7) of the B220+ B cell population of VH3H9/56R, but these B cells are not detectable in either the nontransgenic littermates of this tg (Fig. 1 A) or tgs with anti-DNA H chain transgenes such as 3H9 and 3H9/56R/76R (unpublished data).

Bottom Line: However, the lambda locus, either of man or mouse, does not allow V gene replacement.We have found that in anti-DNA heavy chain transgenic mice (tgs) VH3H9/56R, B cells that express anti-DNA receptors comprised of lambda1 in association with an anti-DNA heavy chain often coexpress a kappa chain that prevents DNA binding.Here we describe a mechanism of preventing DNA binding by expression of a rarely used member of the Vlambda family, Vlambdax.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, Princeton University, NJ 08544, USA. yijinli@uchicago.edu

ABSTRACT
Receptor editing is performed by replacement of Vkappa genes that contribute to autoreactivity. In addition, the Ckappa locus can be deleted by Vkappa rearrangement to intronic or 3' of Ckappa RS sequences (also referred to as kappa deletion elements). B cells that delete the Ckappa can then express lambda light chains. However, the lambda locus, either of man or mouse, does not allow V gene replacement. Nor does it appear to be deleted. Therefore, editing of autoreactive lambda B cells may require alternative pathways. We have found that in anti-DNA heavy chain transgenic mice (tgs) VH3H9/56R, B cells that express anti-DNA receptors comprised of lambda1 in association with an anti-DNA heavy chain often coexpress a kappa chain that prevents DNA binding. We speculate that such isotypically included cells may have low anti-DNA receptor densities, a feature that may lead to self-tolerance. Here we describe a mechanism of preventing DNA binding by expression of a rarely used member of the Vlambda family, Vlambdax. The lambdax B cells of the tgs also express CD25 and may represent B cells that have exhausted light chain editing possibilities.

Show MeSH
Related in: MedlinePlus