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

Carola G. Vinuesa, Yvonne Sunners, Judit Pongracz, Jennifer Ball, Kai Michael Toellner, Dale Taylor, Ian C.M. MacLennan, Matthew C. Cook

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39 Citations (Scopus)


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 cross-linking 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)1340-1350
Number of pages11
JournalEuropean journal of immunology
Issue number5
Publication statusPublished - May 31 2001



  • Antibody formation
  • Bruton's tyrosine kinase
  • CD40 antigen
  • Ficoll
  • Thymus-independent antigen

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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