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Priya, Anshu
Publications (3 of 3) Show all publications
Grundström, C., Kumar, A., Priya, A., Negi, N. & Grundström, T. (2018). ETS1 and PAX5 transcription factors recruit AID to Igh DNA. European Journal of Immunology, 48(10), 1687-1697
Open this publication in new window or tab >>ETS1 and PAX5 transcription factors recruit AID to Igh DNA
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2018 (English)In: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 48, no 10, p. 1687-1697Article in journal (Refereed) Published
Abstract [en]

B lymphocytes optimize antibody responses by class switch recombination (CSR), which changes the expressed constant region exon of the immunoglobulin heavy chain (IgH), and by somatic hypermutation (SH) that introduces point mutations in the variable regions of the antibody genes. Activation-induced cytidine deaminase (AID) is the key mutagenic enzyme that initiates both these antibody diversification processes by deaminating cytosine to uracil. Here we asked the question if transcription factors can mediate the specific targeting of the antibody diversification by recruiting AID. We have recently reported that AID is together with the transcription factors E2A, PAX5 and IRF4 in a complex on key sequences of the Igh locus. Here we report that also ETS1 is together with AID in this complex on key sequences of the Igh locus in splenic B cells of mice. Furthermore, we show that both ETS1 and PAX5 can directly recruit AID to DNA sequences from the Igh locus with the specific binding site for the transcription factor. Taken together, our findings support the notion of a targeting mechanism for the selective diversification of antibody genes with limited genome wide mutagenesis by recruitment of AID by PAX5 and ETS1 in a transcription factor complex.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2018
Keywords
Activation-induced cytidine deaminase, Class switch recombination, Protein interactions, Somatic hypermutation, Transcription factors
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-152886 (URN)10.1002/eji.201847625 (DOI)000446431600008 ()30089192 (PubMedID)
Funder
Swedish Cancer SocietySwedish Research Council
Available from: 2018-10-31 Created: 2018-10-31 Last updated: 2018-10-31Bibliographically approved
Kumar, A., Priya, A., Ahmed, T., Grundström, C., Negi, N. & Grundström, T. (2018). Regulation of the DNA Repair Complex during Somatic Hypermutation and Class-Switch Recombination. Journal of Immunology, 200(12), 4146-4156
Open this publication in new window or tab >>Regulation of the DNA Repair Complex during Somatic Hypermutation and Class-Switch Recombination
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2018 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 200, no 12, p. 4146-4156Article in journal (Refereed) Published
Abstract [en]

B lymphocytes optimize Ab responses by somatic hypermutation (SH), which introduces pointmutations in the variable regions of the Ab genes and by class-switch recombination (CSR), which changes the expressed C region exon of the IgH. These Ab diversification processes are initiated by the deaminating enzyme activation-induced cytidine deaminase followed by many DNA repair enzymes, ultimately leading to deletions and a high mutation rate in the Ab genes, whereas DNA lesions made by activation-induced cytidine deaminase are repaired with low error rate on most other genes. This indicates an advanced regulation of DNA repair. In this study, we show that initiation of Ab diversification in B lymphocytes of mouse spleen leads to formation of a complex between many proteins in DNA repair. We show also thatBCR activation, which signals the end of successful SH, reduces interactions between some proteins in the complex and increases other interactions in the complex with varying kinetics. Furthermore, we show increased localization of SH-and CSR-coupled proteins on switch regions of the Igh locus upon initiation of SH/CSR and differential changes in the localization upon BCR signaling, which terminates SH. These findings provide early evidence for a DNA repair complex or complexes that may be of functional significance for carrying out essential roles in SH and/or CSR in B cells.

Place, publisher, year, edition, pages
American Association of Immunologists, 2018
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-151570 (URN)10.4049/jimmunol.1701586 (DOI)000442386300029 ()29728513 (PubMedID)
Funder
Swedish Cancer SocietySwedish Research Council
Available from: 2018-09-10 Created: 2018-09-10 Last updated: 2018-09-10Bibliographically approved
Grundström, T., Hauser, J., Grundström, C., Kumar, A., Priya, A. & Kumar, R. (2016). Regulation of diversification and affinity maturation of antibodies. International Journal of Molecular Medicine, 38, S43-S43
Open this publication in new window or tab >>Regulation of diversification and affinity maturation of antibodies
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2016 (English)In: International Journal of Molecular Medicine, ISSN 1107-3756, E-ISSN 1791-244X, Vol. 38, p. S43-S43Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Spandidos, 2016
National Category
Basic Medicine
Identifiers
urn:nbn:se:umu:diva-126770 (URN)000383733000154 ()
Note

Supplement: 1, Meeting Abstract: 253

Available from: 2016-10-18 Created: 2016-10-13 Last updated: 2018-06-09Bibliographically approved
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