title: B cell depletion in immune thrombocytopenia reveals splenic long-lived plasma cells.
abstract: 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.
authors.affiliation: Faculté de Médecine, Site Necker-Enfants Malades, INSERM U783 Développement du système immunitaire, Université Paris Descartes, Paris, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Mahévas
authors.forename: Pauline
authors.initials: P
authors.lastname: Patin
authors.forename: François
authors.initials: F
authors.lastname: Huetz
authors.forename: Marc
authors.initials: M
authors.lastname: Descatoire
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cagnard
authors.forename: Christine
authors.initials: C
authors.lastname: Bole-Feysot
authors.forename: Simon
authors.initials: S
authors.lastname: Le Gallou
authors.forename: Mehdi
authors.initials: M
authors.lastname: Khellaf
authors.forename: Olivier
authors.initials: O
authors.lastname: Fain
authors.forename: David
authors.initials: D
authors.lastname: Boutboul
authors.forename: Lionel
authors.initials: L
authors.lastname: Galicier
authors.forename: Mikael
authors.initials: M
authors.lastname: Ebbo
authors.forename: Olivier
authors.initials: O
authors.lastname: Lambotte
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hamidou
authors.forename: Philippe
authors.initials: P
authors.lastname: Bierling
authors.forename: Bertrand
authors.initials: B
authors.lastname: Godeau
authors.forename: Marc
authors.initials: M
authors.lastname: Michel
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Weill
authors.forename: Claude-Agnès
authors.initials: CA
authors.lastname: Reynaud
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D001323:Autoantibodies / Q000097:blood; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D060885:Multiplex Polymerase Chain Reaction; D010950:Plasma Cells / Q000378:metabolism* / Q000473:pathology; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D000069283:Rituximab; D013154:Spleen / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D013156:Splenectomy; D013997:Time Factors; D059467:Transcriptome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D007155:Immunologic Factors; D000069283:Rituximab