CD19 signaling is impaired in murine peritoneal and splenic B-1 B lymphocytes

Trivikram Dasu, Vishal Sindhava, Stephen H. Clarke, Subbarao Bondada

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

B-1 cells reside predominantly within the coelomic cavities, tonsils, Peyer's patches, spleen (a minor fraction - ∼5%) and are absent in the lymph nodes. They are the primary sources of natural IgM in the body. B-1 cells express polyreactive B cell receptors (BCRs) that cross react with self-antigens and are thus implicated in auto-immune disorders. Previously, we reported that peritoneal B-1 cells are deficient in CD19-mediated intracellular signals leading to Ca2+ mobilization. Here, we find that splenic B-1 cells, like peritoneal B-1 cells, are defective in Ca2+ release upon B cell activation by co-cross-linking BCR and CD19. In the absence of extracellular sources of Ca2+, intracellular Ca2+ flux is similar between B-1 and B-2 cells. Moreover, the intracellular component of Ca2+ release in both subsets of B cells is mostly PI3K dependent. BCR and CD19 co-cross-linking activates Akt, a key mediator of survival and proliferation signals downstream of PI3K in splenic B-2 cells. Splenic B-1 cells, on the other hand, do not phosphorylate Akt (S473) upon similar treatment. Furthermore, BCR + CD19 cross-linking induced phosphorylation of JNK is much reduced in splenic B-1 cells. In contrast, B-1 cells exhibited increased levels of constitutively active pLyn which appears to have an inhibitory role. The CD19 induced Ca2+ response and BCR induced proliferation response were restored by a partial inhibition of pLyn with Src kinase specific inhibitors. These findings suggest a defect in CD19-mediated signals in both peritoneal and splenic B-1 B lymphocytes, which is in part, due to higher levels of constitutively active Lyn.

Original languageEnglish
Pages (from-to)2655-2665
Number of pages11
JournalMolecular Immunology
Volume46
Issue number13
DOIs
StatePublished - Aug 2009

Keywords

  • B cell receptor
  • CD19 signaling
  • Mouse B-1 cells

ASJC Scopus subject areas

  • Immunology
  • Molecular Biology

Fingerprint

Dive into the research topics of 'CD19 signaling is impaired in murine peritoneal and splenic B-1 B lymphocytes'. Together they form a unique fingerprint.

Cite this