B cell Rab7 mediates induction of activation-induced cytidine deaminase expression and class-switching in T-dependent and T-independent antibody responses.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Egest J PonePaolo Casali

Abstract

Class switch DNA recombination (CSR) is central to the maturation of the Ab response because it diversifies Ab effector functions. Like somatic hypermutation, CSR requires activation-induced cytidine deaminase (AID), whose expression is restricted to B cells, as induced by CD40 engagement or dual TLR-BCR engagement (primary CSR-inducing stimuli). By constructing conditional knockout Igh(+/C)γ(1-cre)Rab7(fl/fl) mice, we identified a B cell-intrinsic role for Rab7, a small GTPase involved in intracellular membrane functions, in mediating AID induction and CSR. Igh(+/C)γ(1-cre)Rab7(fl/fl) mice displayed normal B and T cell development and were deficient in Rab7 only in B cells undergoing Igh(C)γ(1-cre) Iγ1-Sγ1-Cγ1-cre transcription, as induced--like Igh germline Iγ1-Sγ1-Cγ1 and Iε-Sε-Cε transcription--by IL-4 in conjunction with a primary CSR-inducing stimulus. These mice could not mount T-independent or T-dependent class-switched IgG1 or IgE responses while maintaining normal IgM levels. Igh(+/C)γ(1-cre)Rab7(fl/fl) B cells showed, in vivo and in vitro, normal proliferation and survival, normal Blimp-1 expression and plasma cell differentiation, as well as intact activation of the noncanonical NF-κB, p38 kinase, and ERK1/2 kinase ...Continue Reading

References

Aug 10, 2000·Immunity·D A FrumanO N Witte
Oct 2, 2004·Nature Reviews. Immunology·Gail A Bishop
Jun 7, 2005·Nature·Yasuhide OhinataM Azim Surani
May 3, 2006·Proceedings of the National Academy of Sciences of the United States of America·Stefano CasolaKlaus Rajewsky
May 16, 2006·Nature Cell Biology·Katia AncelinM Azim Surani
Jan 24, 2007·Immunity·Victoria Menéndez-Benito, Jacques Neefjes
Apr 25, 2007·The Journal of Experimental Medicine·Elizabeth E CrouchRafael Casellas
Jan 12, 2008·Autophagy·Brian C MillerHerbert W Virgin
Jan 30, 2008·Nature Reviews. Genetics·François Leulier, Bruno Lemaitre
Apr 22, 2008·Nature Cell Biology·Jason M KinchenKodi S Ravichandran
Jul 16, 2008·Biochemical and Biophysical Research Communications·Kozo WatanabeTakeshi Tsubata
Mar 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Fei Li KuangMatthew D Scharff
Apr 22, 2009·Nature Immunology·Herbert W Virgin, Beth Levine
Apr 24, 2009·Molecular Biology of the Cell·Kimberly Romero RosalesAimee L Edinger
May 16, 2009·BMC Evolutionary Biology·Paweł Mackiewicz, Elzbieta Wyroba
Aug 29, 2009·Seminars in Immunology·Gail A Bishop
Oct 21, 2009·Nature Immunology·Rebecca K DelkerF Nina Papavasiliou
Feb 23, 2010·Immunity·Heung Kyu LeeAkiko Iwasaki
May 21, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marian L TurnerPhilip D Hodgkin
Jun 1, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shahram MisaghiAli A Zarrin
Jul 21, 2010·Nature Immunology·Christopher C GoodnowRobert Brink
Aug 24, 2010·Nature Structural & Molecular Biology·Zhenming XuPaolo Casali
Dec 9, 2010·Proceedings of the National Academy of Sciences of the United States of America·Andre StanlieNasim A Begum
Dec 15, 2010·Nature Immunology·Robert W MaulPatricia J Gearhart
Jan 21, 2011·Physiological Reviews·Alex H Hutagalung, Peter J Novick
Jan 21, 2011·Nature·Beth LevineHerbert W Virgin
Apr 21, 2011·Science Signaling·David M Allman, Michael P Cancro
Sep 20, 2011·Seminars in Immunology·Stephen L NuttPhilip D Hodgkin
Nov 15, 2011·Cell·Noboru Mizushima, Masaaki Komatsu
Nov 15, 2011·Cell·Ivan ZanoniJonathan C Kagan
Dec 7, 2011·The Journal of Experimental Medicine·Duane R WesemannFrederick W Alt
Dec 14, 2011·Nature Reviews. Immunology·Michael McHeyzer-WilliamsLouise McHeyzer-Williams

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Citations

Oct 16, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tonika LamZhenming Xu
Jan 15, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hui YanZhenming Xu
Nov 23, 2018·Cells·Yoshihiko Kuchitsu, Mitsunori Fukuda
Apr 27, 2019·Frontiers in Immunology·Laleh KhodadadiFalk Hiepe

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