B cell depletion in immune thrombocytopenia reveals splenic long-lived plasma cells.

Matthieu Mahévas (1, 2) , Pauline Patin (1) , François Huetz (1, 3) , Marc Descatoire (1) , Nicolas Cagnard (4) , Christine Bole-Feysot (5) , Simon Le Gallou (1) , Mehdi Khellaf (2) , Olivier Fain (6) , David Boutboul (7) , Lionel Galicier (7) , Mikael Ebbo (8) , Olivier Lambotte (9) , Mohamed Hamidou (10) , Philippe Bierling (11) , Bertrand Godeau (2) , Marc Michel (2) , Jean-Claude Weill (1) , Claude-Agnès Reynaud (1)

1 Développement du Systeme Immunitaire
2 Service de médecine interne [Mondor]
3 Biologie des Populations Lymphocytaires
4 plateforme de bioinformatique
5 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
6 service de médecine interne
7 Service d'Immunopathologie [Hôpital Saint-Louis, Paris]
8 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]
9 service de médecine interne
10 Service de médecine interne [Nantes]
11 etablissement francais du sang

Primary immune thrombocytopenia (ITP) is a disorder caused by autoantibody-mediated platelet destruction and decreased platelet production. Rituximab, a B cell-depleting agent, has become the first-line treatment for ITP; however, patients with refractory disease usually require splenectomy. We identified antibody-secreting cells as the major splenic B cell population that is resistant to rituximab. The phenotype, antibody specificity, and gene expression profile of these cells were characterized and compared to those of antibody-secreting cells from untreated ITP spleens and from healthy tissues. Antiplatelet-specific plasma cells (PC) were detected in the spleens of patients with ITP up to 6 months after rituximab treatment, and the PC population displayed a long-lived program similar to the one of bone marrow PC, thus explaining for most of these patients the absence of response to rituximab and the response to splenectomy. When analyzed by multiplex PCR at the single-cell level, normal splenic PC showed a markedly different gene expression profile, with an intermediate signature, including genes characteristic of both long-lived PC and proliferating plasmablasts. Surprisingly, long-lived PC were not detected in untreated ITP spleens. These results suggest that the milieu generated by B cell depletion promotes the differentiation and settlement of long-lived PC in the spleen.

Domains: Immunology

Matthieu Mahévas, Pauline Patin, François Huetz, Marc Descatoire, Nicolas Cagnard, et al.. B cell depletion in immune thrombocytopenia reveals splenic long-lived plasma cells.. Journal of Clinical Investigation, 2013, 123 (1), pp.432-42. ⟨10.1172/JCI65689⟩. ⟨pasteur-00778075⟩