Tracking the response of Xid B cells in vivo: TI-2 antigen induces migration and proliferation but Btk is essential for terminal differentiation

Carola Garcia de Vineusa de la Concha, Y Sunners, Judit Pongra'cz, J Ball, Kai-Michael Toellner, Dale Taylor, Ian MacLennan, Matthew Cook

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

X-linked immunodeficient (Xid) mice carry a Bruton's tyrosine kinase (Btk) mutation and exhibit a selective failure to produce antibodies against bacterial capsular polysaccharides. Studies in vitro point to a fundamental survival defect of Xid B cells after receptor crosslinking by thymus-independent type-2 (TI-2) antigen because B cells undergo apoptosis without proliferating. We describe results from a novel model, which we have used to investigate the impact of the Xid mutation on migration, proliferation and differentiation of B cells after polysaccharide immunization in vivo. Immunoglobulin knock-in mice, in which a large proportion of B cells express transgene-encoded receptors specific for (4-hydroxy-3-nitrophenyl)-acetyl (NP), were crossed with CBA/N mice. The male progeny contain NP-specific Xid B cells, while the female progeny contain NP-specific B cells with normal Btk. After immunization with the TI-2 antigen NP-Ficoll, NP-specific Xid B cells migrate to the T zones and proliferate. Despite transient up-regulation of blimp-1 and survival beyond the time when terminal differentiation is normally underway, Btk-defective B cells fail to differentiate to plasmablasts or germinal center cells. CD40 ligation partially restores their ability to form plasma cells in response to TI-2 antigen.
Original languageEnglish
Pages (from-to)1340-50
Number of pages11
JournalEuropean Journal of Immunology
Volume31
Issue number5
DOIs
Publication statusPublished - 1 May 2001

Keywords

  • CD40 Antigen
  • thymus-independent antigen
  • ficoll
  • antibody formation
  • Bruton's tyrosine kinase

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