A new role of CTLA-4 on B cells in thymus-dependent immune responses in vivo

J Immunol. 2007 Dec 1;179(11):7316-24. doi: 10.4049/jimmunol.179.11.7316.


The expression of CTLA-4 (CD152) on the cell surface of B cells and its consequences for the humoral immune response in vivo are unknown. We investigated the expression of CTLA-4 mRNA and protein in B cells in T cell-independent or -dependent ways. B cells in the presence of Ag-stimulated Th2 cells expressed mRNA of CTLA-4 and up-regulated intracellular CTLA-4 protein. Using a liposome-enhanced staining technique, we show for the first time, that surface CTLA-4 protein is expressed by 11-15% of B cells in a T cell-dependent culture system. To dissect the role of CTLA-4 on B cells in vivo, we used bone marrow chimeric mice in which only B cells were CTLA-4 deficient. These mice showed that early B cell development and homeostasis is not influenced by CTLA-4 deficiency of B cells. Ag-specific responses after immunization of the chimeric mice revealed elevated levels of IgM Abs in mice deficient for B cell CTLA-4. We propose that CTLA-4 signals on B cells determine the early fate of B cells in thymus-dependent immune responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / biosynthesis
  • Antigens, CD / physiology*
  • Antigens, Differentiation / biosynthesis
  • Antigens, Differentiation / physiology*
  • B-Lymphocytes / immunology*
  • CTLA-4 Antigen
  • Cells, Cultured
  • Immunization
  • Immunoglobulin E / immunology
  • Immunoglobulin M / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • RNA, Messenger / biosynthesis
  • T-Lymphocytes / immunology*
  • Thymus Gland / immunology*


  • Antigens, CD
  • Antigens, Differentiation
  • CTLA-4 Antigen
  • Ctla4 protein, mouse
  • Immunoglobulin M
  • RNA, Messenger
  • Immunoglobulin E