Sequence of the Lyb-2 B-cell differentiation antigen defines a gene superfamily of receptors with inverted membrane orientation

Abstract Lyb-2 is a mouse B-cell differentiation antigen expressed on the surface of pre-B cells and B cells but not on terminally differentiated antibody-secreting plasma cells. Lyb-2 has been shown to play a role in B-cell activation and differentiation and may be a receptor for a B-cell growth factor or lymphokine. We have isolated and sequenced cDNA encoding the Lyb-2.1 allele. Lyb-2 mRNA is expressed only in B-lineage cells and is absent from antibody-secreting cell lines. The predicted protein contains 354 amino acids and is lacking an amino-terminal signal peptide. The protein is shown to be oriented with its carboxyl terminus external to the cell. Sequence comparisons demonstrate that Lyb-2 is homologous to the asialoglycoprotein receptor and to CD23, the B-cell-specific Fc receptor for IgE, both of which are oriented with their carboxyl termini external to the cell. These molecules, therefore, constitute a gene superfamily of cell surface receptors with inverted membrane orientation.