V<sub>λ</sub>‐J<sub>λ</sub> rearrangements are restricted within a V‐J‐C recombination unit in the mouse

Sanchez, Pierre; Nadel, Bertrand; Cazenave, Pierre‐André

doi:10.1002/eji.1830210408

Cited by 42 publications

(34 citation statements)

References 43 publications

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“…5B). No serum V x was detectable in C.B-17 scid/ϩ mice, the nontransgenic control (our unpublished results), consistent with previous reports of little or no detectable V x protein in normal mice (28,50). To test whether the T3 and T3Ј subsets contained cells able to differentiate into V x-producing plasma cells, we transferred sorted T3 and T3Ј cells into SCID recipients in the manner previously described (24).…”

Section: Detection Of L Chain-edited B Cells In Spl But Not Bm Of 56rsupporting

confidence: 86%

Antigen Receptor Editing in Anti-DNA Transitional B Cells Deficient for Surface IgM

Kiefer

Nakajima

Oshinsky

et al. 2008

The Journal of Immunology

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In response to encounter with self-Ag, autoreactive B cells may undergo secondary L chain gene rearrangement (receptor editing) and change the specificity of their Ag receptor. Knowing at what differentiative stage(s) developing B cells undergo receptor editing is important for understanding how self-reactive B cells are regulated. In this study, in mice with Ig transgenes coding for anti-self (DNA) Ab, we report dsDNA breaks indicative of ongoing secondary L chain rearrangement not only in bone marrow cells with a pre-B/B cell phenotype but also in immature/transitional splenic B cells with little or no surface IgM (sIgM−/low). L chain-edited transgenic B cells were detectable in spleen but not bone marrow and were still found to produce Ab specific for DNA (and apoptotic cells), albeit with lower affinity for DNA than the unedited transgenic Ab. We conclude that L chain editing in anti-DNA-transgenic B cells is not only ongoing in bone marrow but also in spleen. Indeed, transfer of sIgM−/low anti-DNA splenic B cells into SCID mice resulted in the appearance of a L chain editor (Vλx) in the serum of engrafted recipients. Finally, we also report evidence for ongoing L chain editing in sIgMlow transitional splenic B cells of wild-type mice.

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Section: Detection Of L Chain-edited B Cells In Spl But Not Bm Of 56rsupporting

confidence: 86%

Antigen Receptor Editing in Anti-DNA Transitional B Cells Deficient for Surface IgM

Kiefer

Nakajima

Oshinsky

et al. 2008

The Journal of Immunology

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“…The mouse locus has two separate clusters, each consisting of V and JC gene segments (Fig. 3 Middle) (15,16). In one cluster, V1 rearranges either to J1 or J3.…”

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confidence: 99%

“…In one cluster, V1 rearranges either to J1 or J3. In the other cluster, V2 or VX rearranges to J2 (15). Rearrangements that leapfrog across clusters (for example, V2 to J1) are very infrequent (15).…”

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confidence: 99%

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Consequences of receptor editing at the λ locus: Multireactivity and light chain secretion

Doyle

Han²,

Weigert

et al. 2006

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

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To investigate the manner in which B cells with light (L) chains undergo receptor editing, we have studied hybridoma panels from 56R͞-deleted (kdel) mice. 56R͞kdel mice only produce four L chains (1, 2, 3, and X). They also have a simplified heavy (H) chain repertoire: All B cells start out with a 56R anti-DNA H chain. A few frankly autoreactive 56R 1 cells appear to escape into the periphery, but the majority of the peripheral B cell repertoire in 56R͞kdel is made up of B cells expressing the 56R H chain with the X L chain. Surprisingly, 56R X B cells are multireactive, binding to a variety of self and nonself antigens, including dsDNA (albeit at reduced affinity compared with the other L chains). Another significant population in the 56R͞kdel mouse consists of allelically included B cells that express X along with another L chain. The multireactivity of both 56R X and 56R X͞1 receptors could contribute to autoimmunity if these B cells were to become activated. Also found among 56R͞kdel hybridomas are clones that have inactivated the H chain and secrete only L chains. These clones may represent products of exhaustive rearrangement. Multireactivity, allelic inclusion, and L chain secretion are three consequences of editing at the locus that may predispose toward the development of autoimmunity.olerance to self-antigens can be achieved by replacing autoreactive heavy (H) chain and light (L) chain V genes with V genes coding for nonself receptors, a mechanism called receptor editing (1-4). Several recent studies support a pivotal role for receptor editing in the generation of a tolerant B cell repertoire (5-7). The L chain locus uses the nested organization of V and J gene segments for secondary rearrangements that can replace or inactivate a VJ that contributes to autoreactivity ( Fig. 3 Top, which is published as supporting information on the PNAS web site). editing can also delete and͞or inactivate an autoreactive chain by rearrangement to the de (human) or to RS (mouse) (8-10). Secondary rearrangements to J and deleting elements are presumed to be unidirectional; hence, editing enriches the repertoire in J5 rearrangements. Editing also increases the frequency of B cells that are rearranged at both alleles (3,(11)(12)(13). Rearrangement at the second L chain isotype, , can rescue -inactivated and -deleted B cells (1,14).L chain genes also contribute to autoreactivity and require editing. The mouse locus has two separate clusters, each consisting of V and JC gene segments (Fig. 3 Middle) (15, 16). In one cluster, V1 rearranges either to J1 or J3. In the other cluster, V2 or VX rearranges to J2 (15). Rearrangements that leapfrog across clusters (for example, V2 to J1) are very infrequent (15). Thus a B cell with a rearrangement that yields a self-reactive receptor is in a dangerous position because of its inability to delete the primary rearrangement.H chain variable region gene segment (V H ) genes can also be edited because a VDJ gene can be replaced by secondary rearrangement of an upstream V H to a partial RS...

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“…It spans only 240 kb on chromosome 16 and contains two gene clusters that appear to have arisen by duplication (reviewed by [5]). Each cluster contains 1-2 variable gene segments followed by two joining/constant (J/C) regions, in the order V 2 -V x -JC 2 -JC 4 --V 1 -JC 3 -JC 1 [6,7]; since JC 4 is a pseudogene, the locus undergoes only four main rearrangements: V 1 -J 1 , V 2 -J 2 V x -J 2 and V 1 -J 3 that occur in the ratio 3:2:2:1 [8,9]. However, V 2 can also recombine with JC 1 or JC 3 , albeit infrequently [10].…”

Section: Introductionmentioning

confidence: 99%

The Eλ3–1 enhancer is essential for V(D)J recombination of the murine immunoglobulin lambda light chain locus

Haque¹,

Bevington²,

Boyes³

2013

Biochemical and Biophysical Research Communications

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V_λ‐J_λ rearrangements are restricted within a V‐J‐C recombination unit in the mouse

Cited by 42 publications

References 43 publications

Antigen Receptor Editing in Anti-DNA Transitional B Cells Deficient for Surface IgM

Antigen Receptor Editing in Anti-DNA Transitional B Cells Deficient for Surface IgM

Consequences of receptor editing at the λ locus: Multireactivity and light chain secretion

The Eλ3–1 enhancer is essential for V(D)J recombination of the murine immunoglobulin lambda light chain locus

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Vλ‐Jλ rearrangements are restricted within a V‐J‐C recombination unit in the mouse

Cited by 42 publications

References 43 publications

Antigen Receptor Editing in Anti-DNA Transitional B Cells Deficient for Surface IgM

Antigen Receptor Editing in Anti-DNA Transitional B Cells Deficient for Surface IgM

Consequences of receptor editing at the λ locus: Multireactivity and light chain secretion

The Eλ3–1 enhancer is essential for V(D)J recombination of the murine immunoglobulin lambda light chain locus

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Product

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V_λ‐J_λ rearrangements are restricted within a V‐J‐C recombination unit in the mouse