Influence of <i>xid</i> on Anti-Azophenylarsonate (Ar) Antibody Responses of (CBA/N × A/J)F₁ Mice: Differential Idotype Expression Induced by Only One of Two Ar Antigens

Abstract

The influence of an X chromosome-linked immune deficiency gene (xid) on several properties of the anti-azophenylarsonate (Ar) antibody responses of (CBA/N × A/J)F₁ (NAF₁) mice was examined. With respect to response magnitude, it was found that male, xid-expressing NAF₁ mice showed about 1/3 the concentration of serum anti-Ar antibody as normal female NAF₁ mice in hyperimmune responses to Brucella abortus (BA)-Ar. In responses induced by keyhole limpet hemoycanin (KLH)-Ar, males showed responses of about 1/8 to 1/2 the female levels, depending on the assay time point. The kinetics of the latter response were identical in mice of the two sexes. No significant difference could be detected in the time-dependent avidity maturation of the anti-Ar antibody elicited by KLH-Ar in xid vs. normal mice. The isotype profile of the day 38 anti-Ar primary response elicited by KLH-Ar in male NAFi mice differed from that of the female mice in two ways: (1) IgG_2a levels were depressed, and (2) a significantly lower number of the male mice demonstrated detectable IgG₃ anti-Ar antibody production. The primary focus of this work was to determine the effect of xid on the expression of the major cross-reactive idiotype – CRI_A – of A strain mice. It was found that while a significantly higher proportion of the female mice could be classified as high CRU producers in responses to BA-Ar, no difference could be demonstrated if the inducing antigen was KLH-Ar. It is proposed that the difference observed with the two antigens may be due to the more selective activation by KLH-Ar of a small subset of high affinity Ar-specific clones – which may be enriched for CRI_A + precursors – in both normal and immune defective mice. In contrast, BA-Ar may ‘sample’ more of the total anti-Ar repertoire and thus reveal within it an xid-determined depression in the proportion of CRI_A + clones. Finally, it is noted that the influence of xid appears to be largely of a stochastic, and not an absolute character.