LAT links the pre-BCR to calcium signaling

Immunity. 2003 Aug;19(2):295-305. doi: 10.1016/s1074-7613(03)00202-4.

Abstract

SLP-65(-/-) mice display a partial block at the pre-B cell stage of development. Here, we show that LAT is required for the differentiation of SLP-65(-/-) pre-B cells. We show that LAT and SLP-76 are recruited to the pre-BCR and associated with Ig-alpha upon pre-BCR engagement, whereas LAT interaction with SLP-76 is already detected in untreated pre-B cells. Reconstitution of LAT or SLP-65 expression in SLP-65/LAT(-/-) pre-B cells restored their calcium (Ca2+) mobilization capacity, led to downregulation of surface pre-BCR, and induced differentiation to BCR+ cells. Together, our results suggest that the adaptor proteins LAT and SLP-76 are involved in pre-BCR signaling, thereby rescuing arrested murine SLP-65(-/-) pre-B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Antigens, CD / metabolism
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism*
  • CD79 Antigens
  • Calcium Signaling / physiology*
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology*
  • Cell Differentiation
  • Down-Regulation
  • In Vitro Techniques
  • Membrane Proteins*
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Phospholipase C gamma
  • Phosphoproteins / deficiency
  • Phosphoproteins / genetics
  • Phosphoproteins / immunology*
  • Receptors, Antigen, B-Cell / metabolism*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Type C Phospholipases / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • B cell linker protein
  • CD79 Antigens
  • Carrier Proteins
  • Cd79a protein, mouse
  • Lat protein, mouse
  • Membrane Proteins
  • Phosphoproteins
  • Receptors, Antigen, B-Cell
  • Type C Phospholipases
  • Phospholipase C gamma