Receptor Editing Occurs Frequently During Normal B Cell Development

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1998 Oct 9

PMID 9763602

Citations 70

Authors

M W Retter

D Nemazee

Affiliations

Soon will be listed here.

Abstract

Allelic exclusion is established in development through a feedback mechanism in which the assembled immunoglobulin (Ig) suppresses further V(D)J rearrangement. But Ig expression sometimes fails to prevent further rearrangement. In autoantibody transgenic mice, reactivity of immature B cells with autoantigen can induce receptor editing, in which allelic exclusion is transiently prevented or reversed through nested light chain gene rearrangement, often resulting in altered B cell receptor specificity. To determine the extent of receptor editing in a normal, non-Ig transgenic immune system, we took advantage of the fact that lambda light chain genes usually rearrange after kappa genes. This allowed us to analyze kappa loci in IgMlambda+ cells to determine how frequently in-frame kappa genes fail to suppress lambda gene rearrangements. To do this, we analyzed recombined VkappaJkappa genes inactivated by subsequent recombining sequence (RS) rearrangement. RS rearrangements delete portions of the kappa locus by a V(D)J recombinase-dependent mechanism, suggesting that they play a role in receptor editing. We show that RS recombination is frequently induced by, and inactivates, functionally rearranged kappa loci, as nearly half (47%) of the RS-inactivated VkappaJkappa joins were in-frame. These findings suggest that receptor editing occurs at a surprisingly high frequency in normal B cells.

Citing Articles

Kidins220 regulates the development of B cells bearing the λ light chain.

Schaffer A, Fiala G, Hils M, Natali E, Babrak L, Herr L Elife. 2024; 13.

PMID: 38271217 PMC: 10810608. DOI: 10.7554/eLife.83943.

Asymmetrical forward and reverse developmental trajectories determine molecular programs of B cell antigen receptor editing.

Okoreeh M, Kennedy D, Olumide Emmanuel A, Veselits M, Moshin A, Ladd R Sci Immunol. 2022; 7(74):eabm1664.

PMID: 35930652 PMC: 9636592. DOI: 10.1126/sciimmunol.abm1664.

A case of solitary plasmacytoma of bone showing co-expression of both immunoglobulin light chains.

Matsuoka R, Sakamoto N, Kato T, Chiba S, Noguchi M Eur J Med Res. 2021; 26(1):148.

PMID: 34930458 PMC: 8686560. DOI: 10.1186/s40001-021-00621-8.

Immunoglobulin Light Chain Gene Rearrangements, Receptor Editing and the Development of a Self-Tolerant Antibody Repertoire.

Collins A, Watson C Front Immunol. 2018; 9:2249.

PMID: 30349529 PMC: 6186787. DOI: 10.3389/fimmu.2018.02249.

Foxo3 Promotes Apoptosis of B Cell Receptor-Stimulated Immature B Cells, Thus Limiting the Window for Receptor Editing.

Ottens K, Hinman R, Barrios E, Skaug B, Davis L, Li Q J Immunol. 2018; 201(3):940-949.

PMID: 29950509 PMC: 6057821. DOI: 10.4049/jimmunol.1701070.

References

Kearney J, Radbruch A, Liesegang B, Rajewsky K . A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines. J Immunol. 1979; 123(4):1548-50. View

Ghia P, Gratwohl A, Signer E, Winkler T, Melchers F, Rolink A . Immature B cells from human and mouse bone marrow can change their surface light chain expression. Eur J Immunol. 1995; 25(11):3108-14. DOI: 10.1002/eji.1830251118. View

Durdik J, Moore M, Selsing E . Novel kappa light-chain gene rearrangements in mouse lambda light chain-producing B lymphocytes. Nature. 1984; 307(5953):749-52. DOI: 10.1038/307749a0. View

Ritchie K, Brinster R, STORB U . Allelic exclusion and control of endogenous immunoglobulin gene rearrangement in kappa transgenic mice. Nature. 1984; 312(5994):517-20. DOI: 10.1038/312517a0. View

Siminovitch K, Bakhshi A, Goldman P, Korsmeyer S . A uniform deleting element mediates the loss of kappa genes in human B cells. Nature. 1985; 316(6025):260-2. DOI: 10.1038/316260a0. View

Moore M, Durdik J, Persiani D, Selsing E . Deletions of kappa chain constant region genes in mouse lambda chain-producing B cells involve intrachromosomal DNA recombinations similar to V-J joining. Proc Natl Acad Sci U S A. 1985; 82(18):6211-5. PMC: 391022. DOI: 10.1073/pnas.82.18.6211. View

Chen C, Prak E, Weigert M . Editing disease-associated autoantibodies. Immunity. 1997; 6(1):97-105. DOI: 10.1016/s1074-7613(00)80673-1. View

Hertz M, Nemazee D . BCR ligation induces receptor editing in IgM+IgD- bone marrow B cells in vitro. Immunity. 1997; 6(4):429-36. DOI: 10.1016/s1074-7613(00)80286-1. View

Retter M, Cohen P, Eisenberg R, Clarke S . Both Sm and DNA are selecting antigens in the anti-Sm B cell response in autoimmune MRL/lpr mice. J Immunol. 1996; 156(3):1296-306. View

10.

Xu Y, Davidson L, Alt F, Baltimore D . Deletion of the Ig kappa light chain intronic enhancer/matrix attachment region impairs but does not abolish V kappa J kappa rearrangement. Immunity. 1996; 4(4):377-85. DOI: 10.1016/s1074-7613(00)80251-4. View

11.

Arakawa H, Shimizu T, Takeda S . Re-evaluation of the probabilities for productive arrangements on the kappa and lambda loci. Int Immunol. 1996; 8(1):91-9. DOI: 10.1093/intimm/8.1.91. View

12.

Gorman J, Van der Stoep N, MONROE R, Cogne M, Davidson L, Alt F . The Ig(kappa) enhancer influences the ratio of Ig(kappa) versus Ig(lambda) B lymphocytes. Immunity. 1996; 5(3):241-52. DOI: 10.1016/s1074-7613(00)80319-2. View

13.

LANG J, Jackson M, Teyton L, Brunmark A, Kane K, Nemazee D . B cells are exquisitely sensitive to central tolerance and receptor editing induced by ultralow affinity, membrane-bound antigen. J Exp Med. 1996; 184(5):1685-97. PMC: 2192881. DOI: 10.1084/jem.184.5.1685. View

14.

Melamed D, Nemazee D . Self-antigen does not accelerate immature B cell apoptosis, but stimulates receptor editing as a consequence of developmental arrest. Proc Natl Acad Sci U S A. 1997; 94(17):9267-72. PMC: 23150. DOI: 10.1073/pnas.94.17.9267. View

15.

Papavasiliou F, Casellas R, Suh H, Qin X, Besmer E, Pelanda R . V(D)J recombination in mature B cells: a mechanism for altering antibody responses. Science. 1997; 278(5336):298-301. DOI: 10.1126/science.278.5336.298. View

16.

Han S, Dillon S, Zheng B, Shimoda M, Schlissel M, Kelsoe G . V(D)J recombinase activity in a subset of germinal center B lymphocytes. Science. 1997; 278(5336):301-5. DOI: 10.1126/science.278.5336.301. View

17.

Pelanda R, Schwers S, Sonoda E, Torres R, Nemazee D, Rajewsky K . Receptor editing in a transgenic mouse model: site, efficiency, and role in B cell tolerance and antibody diversification. Immunity. 1998; 7(6):765-75. DOI: 10.1016/s1074-7613(00)80395-7. View

18.

Melamed D, Benschop R, Cambier J, Nemazee D . Developmental regulation of B lymphocyte immune tolerance compartmentalizes clonal selection from receptor selection. Cell. 1998; 92(2):173-82. DOI: 10.1016/s0092-8674(00)80912-5. View

19.

Hikida M, Ohmori H . Rearrangement of lambda light chain genes in mature B cells in vitro and in vivo. Function of reexpressed recombination-activating gene (RAG) products. J Exp Med. 1998; 187(5):795-9. PMC: 2212171. DOI: 10.1084/jem.187.5.795. View

20.

Hertz M, Nemazee D . Receptor editing and commitment in B lymphocytes. Curr Opin Immunol. 1998; 10(2):208-13. DOI: 10.1016/s0952-7915(98)80250-1. View