Activation of resting B lymphocytes leads to a complex series of events, some of which result in a permanent conversion of the cellular phenotype which clearly distinguishes the differentiated cell from the resting cell. This chapter aims to document some of the better-studied protein changes clearly associated with B cell differentiation. It examines trace the points in the biosynthetic pathway at which these changes are initiated, starting at the genomic level and ending at the level of protein expression. The chapter shows that the alterations of immunoglobulin (Ig) expression during B cell differentiation can result from changes at virtually all levels of gene expression. For the B lymphocyte, the most prominent change incurred after activation is that of Ig secretion. The regulatory basis for alterations in gene expression after B cell activation has been studied in the greatest detail for secretory and membrane Igs.