Defective B - Cell Maturation

The CBA/N strain of mouse, derived in 1966 from the C B A / H strain (1), carries an X-linked mutation whose expression affects a number of B-cell functions. The B cells in adult CBA/N mice have many of the characteristics of those found in neonatal mice, including a higher density of surface IgM and a lower expression of B-cell differentiation markers, such as Ia, Mls, Lyb3, and Lyb5.1 (2-5). In addition, there is a change in the pattern of responsiveness of B cells in these mice to various groups of antigens and mitogens. B-cell polyclonal mitogens (lipopolysaccharide [LPS]) a, thymus-dependent antigens (sheep erythroeytes, [SRBC]), and one group of thymusindependent antigens termed TI-1 (trinitrophenyl [TNP]-LPS and TNP-Brucel la abortus) (6) all stimulate responses in these mice (1, 2, 6-12). In contrast, this strain apparently has a complete lack of responsiveness to a second group of thymusindependent antigens, TI-2 (TNP-Ficoll, Poly I:C, SSS-III) (9, 10, 13-15) which appear to stimulate a more mature population of B cells (6). The possibility exists that there is a relationship between the pattern of surface-marker expression and the pattern of responsiveness to various antigens and mitogens. The purpose of this work is to examine the effect of age on the B-cell response capabilities of CBA/N mice. Although spleen cells from these defective mice respond in vitro to both mitogens and thymus-dependent antigens, the levels of responsiveness reported have varied greatly (1, 2, 6, 10, 14, 16). The experiments described in this paper reveal that responses of CBA/N and (CBA/N × DBA/2)F1 male mice to the mitogen, LPS, and the thymus-dependent antigen, SRBC, increase markedly with age. In addition, spleen cells from these mice show a distinct age-related increase in the percentage of surface Ig + cells. These findings show that the X-linked mutation in the CBA/N mouse affects maturat ion rates of many B-cell functions during a critical time range, which may account for the variability seen in experiments in the reported literature.