CD40 expression and function in murine B cell ontogeny.
The CD40 antigen, a member of the nerve growth factor/tumor necrosis factor receptor family, is expressed on all mature B lymphocytes and plays a crucial role in B cell activation, T cell-dependent antigen-driven isotype switching and germinal center formation. We have analyzed CD40 expression and function during mouse B cell development by examining B cell precursors in normal mice and in transgenic animals in which B cell development is frozen at discrete stages. These models included RAG-2-/- mice, and transgenic littermates that express a mu heavy chain and/or the bcl-2 proto-oncogene transgene. CD40 was undetectable at the pro-B cell stage, but was expressed, although at low levels, on pre-B cells. However, pre-B cells failed to respond to CD40 triggering either by expression of CD23 or by proliferation in the presence of IL-4. Overexpression of bcl-2 increased the density of CD40 expression on pre-B cells: these cells respond to CD40 ligation by expressing CD23 and by proliferating in the presence of IL-4.
Castigli
E
E
Division of Immunology, Children's Hospital, Boston, MA 02115, USA.
Young
F
F
Carossino
A M
AM
Alt
F W
FW
Geha
R S
RS
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001483:Base Sequence; D001853:Bone Marrow / Q000276:immunology; D019013:CD40 Antigens / Q000096:biosynthesis* / Q000276:immunology; D002454:Cell Differentiation; D002455:Cell Division; D005434:Flow Cytometry; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D017455:Receptors, IgE / Q000096:biosynthesis; D013154:Spleen / Q000276:immunology
D019013:CD40 Antigens; D017455:Receptors, IgE