Rap1b regulates B cell development, homing, and T cell-dependent humoral immunity.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Haiyan ChuSubramaniam Malarkannan

Abstract

Rap1 is a small GTPase that belongs to Ras superfamily. This ubiquitously expressed GTPase is a key regulator of integrin functions. Rap1 exists in two isoforms: Rap1a and Rap1b. Although Rap1 has been extensively studied, its isoform-specific functions in B cells have not been elucidated. In this study, using gene knockout mice, we show that Rap1b is the dominant isoform in B cells. Lack of Rap1b significantly reduced the absolute number of B220(+)IgM(-) pro/pre-B cells and B220(+)IgM(+) immature B cells in bone marrow. In vitro culture of bone marrow-derived Rap1b(-/-) pro/pre-B cells with IL-7 showed similar proliferation levels but reduced adhesion to stromal cell line compared with wild type. Rap1b(-/-) mice displayed reduced splenic marginal zone (MZ) B cells, and increased newly forming B cells, whereas the number of follicular B cells was normal. Functionally, Rap1b(-/-) mice showed reduced T-dependent but normal T-independent humoral responses. B cells from Rap1b(-/-) mice showed reduced migration to SDF-1, CXCL13 and in vivo homing to lymph nodes. MZ B cells showed reduced sphingosine-1-phosphate-induced migration and adhesion to ICAM-1. However, absence of Rap1b did not affect splenic B cell proliferation, BCR-mediat...Continue Reading

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Citations

Aug 13, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Elizabeth M ToddSharon Celeste Morley
Nov 4, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sreemanti BasuBonnie N Dittel
Apr 19, 2019·Cell Death and Differentiation·Miguel A Galindo-CamposJosé Yélamos
Apr 8, 2020·Inflammation and Regeneration·Naoki Hosen
Aug 25, 2010·The Journal of Experimental Medicine·Aradhana AwasthiSubramaniam Malarkannan
Nov 11, 2015·The Biochemical Journal·Takuro Numaga-TomitaYasuo Mori
Dec 30, 2015·PloS One·Magdalena Chrzanowska-WodnickaKevin J Whitehead
Oct 24, 2015·Reproduction : the Official Journal of the Society for the Study of Fertility·Damián Oscar MuzzioFederico Jensen
May 22, 2016·Blood·Frederic LagarrigueMark H Ginsberg
Mar 27, 2015·EMBO Reports·Sribalaji LakshmikanthanMagdalena Chrzanowska-Wodnicka
Jun 15, 2011·Annual Review of Cell and Developmental Biology·Chungho KimMark H Ginsberg
Jun 19, 2021·Frontiers in Immunology·Sayaka IshiharaKoko Katagiri
Jan 12, 2010·Developmental Biology·E W Frische, F J T Zwartkruis
Feb 8, 2011·Life Sciences·Selvi C JeyarajMaqsood A Chotani

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