Germinal centers are histologically distinct structures that form within the draining lymphoid tissues following immunization with T cell-dependent antigens. Here, antigen-specific B cells transform the lymphoid follicle into a site of intense B cell proliferation, differentiation and selection. To understand the molecular basis for these cellular events, we sought to isolate germinal center B cell-specific genes using subtractive cDNA libraries derived from FACS-sorted (CD45R/B220+, IgD-, Thy1.2-) lymph node B cells of immunized mice. A novel gene isolated from this library, designated M17, was found to be transcribed in spleen and, to a lesser extent, bone marrow. Strikingly, only PNA+ (germinal center) but not PNA- splenic B cells express M17. Germinal center-specific expression of M17 was confirmed by staining of histological sections of spleen with an antiserum raised against a glutathione-S-transferase-M17 fusion protein. The M17 gene comprises four exons spanning 13.2 kb, and encodes a 25 kDa cytoplasmic protein of 159 amino acids. Analysis of the amino acid sequence revealed the presence of a possible lipid binding domain and multiple potential phosphorylation sites, including a tyrosine-based activation motif. We speculate that M17 may be a signaling molecule involved in the transduction of signals from the cell surface to the cytoplasm.