ONTOGENY OF B-LYMPHOCYTE FUNCTION I. Restricted Heterogeneity of the Antibody Response of B Lymphocytes from Neonatal and Fetal Mice* BY EDMOND A. GOIDL AND GREGORY

The adul t ant ibody response is generally characterized by a marked degree of heterogeneity of affinity of the ant ibody for the antigenic de terminant (1, 2). With t ime after immunizat ion there appears to be a preferential selection of high affinity ant ibody-producing B lymphocytes resulting in an increase in the average affinity of the serum ant ibody (2-19). It is usually assumed tha t individual B lymphocytes produce a homogeneous ant ibody product (20) and tha t the heterogeneity of serum ant ibody is a consequence of the st imulation, by antigen, of a number of different B lymphocytes (18). Most workers agree tha t some form of clonal selection theory (21) accounts for the specificity of the immune response. However, the mechanism which gives rise to the diversity of information required to synthesize the large array of different ant ibody molecules which can be formed by the normal adul t animal is not known. Two al ternative theories have been proposed: (a) tha t all information is coded in the germ line or (b) that l imited information is coded in the germ line and that the available diversity is expanded by some process of somatic mutat ion or recombination. Previous studies on the ontogeny of the immune response have suggested tha t there is an ordered progressive development of the abi l i ty to respond to different antigens (22-24). Tlymphocyte function has been shown to mature relatively late in development (25). B lymphocytes or their precursors can be detected relatively early in ontogeny (26-30). It is not clear whether the demonstra ted l imitat ions in the immune response of fetal or neonatal animals reflect a lack of B lymphocytes capable of synthesizing the antibody in quest ion or a lack of development of necessary antigen "processing" or "localizing" mechanisms.