Partial reconstitution of TNP-Ficoll responses and IgG3 expression in Xid mice undergoing graft-<i>vs</i>-host reaction.

Abstract

Abstract We showed previously that primary responses to T-dependent (TD) and T-independent type 2 (TI-2) antigens were differentially affected by allogeneic effects induced in vivo during a graft-vs-host reaction (GVH). TD responses were suppressed 80% or more whereas TI-2 responses were greatly enhanced, particularly the IgG component, which normally is very low. Isotype analysis of the augmented TI-2 responses showed a marked increase in all four IgG subclasses with an apparent shift from lgG3 to lgG1 dominance in the spleen. This augmentation could have resulted from recruitment of additional precursors from a pool of less mature B1 precursors. This hypothesis was examined in Xid (CBA/N × BALB/c)F1 male mice that are deficient in TI-2 responding B cells and have low levels of serum IgM and lgG3. It was found that (CBA/N × BALB/c)F1 males produced significant numbers of TNP-specific PFC and serum antibodies if injected with parental T cells (of either BALB/c or CBA/N origin) shortly before TNP-Ficoll administration. From 30 to 40% of this response was of the lgG3 subclass. Similarly, TNP-KLH-primed F1-Xid males, which normally can give secondary responses only to TD and TI-1 but not to TI-2 antigens, were found to possess memory that could be elicited by TNP-Ficoll shortly after induction of GVH. These B1 memory responses were characterized by high IgG/IgM ratios and by IgGl subclass predominance. No B colony-forming cells were detected in spleens of GVH F1 males indicating that GVH by itself did not induce generalized maturation of the defective B cell lineage in Xid mice. We conclude that Xid mice contain a pool of immature B1 precursors that can be driven into later stages of differentiation by the relevant antigens acting in concert with strong nonspecific T cell signals.