Cellular and molecular requirements for X-linked, hapten-specific B-cell blockade in CBA/N mice.
CBA/N mice, a mutant CBA subline, harbor an X-linked B-cell defect which prevents them from mounting immune responses to certain thymic-independent antigens such as pneumococcal polysaccharides and haptenated-Ficoll derivatives. These mice and the hybrid male progeny of CBA/N females are also exquisitely sensitive to a hapten-specific blockade of their otherwise adequate immune responses to thymic-dependent antigens such as N-2,4-dinitrophenylated-hemocyanin (DNP-KLH). As little as 10 ng of a DNP-Ficoll conjugate given 2 h before immunization with a 5,000-fold greater dosage of DNP-KLH, virtually abolishes the 4th-day direct plaque-forming cell (PFC) response specific for DNP. Responding hybrid (CBA/N x C3H/HeN) female mice are resistant to such blockade even at DNP-Ficoll dosages increased by three orders of magnitude. The DNP hapten and Ficoll must be chemically joined for this blocking effect to occur, and increasing the hapten derivatization of Ficoll increases its blockade-invoking capacity. Significant blockade can be produced by administering DNP-Ficoll as early as 4 days before or as late as 4 h after immunization with DNP-KLH. All currently available data point to the defective B cell as the target of this hapten-polysaccharide-mediated blockade. Mice bearing B memory cells, however, are refractory to such blockade. In addition, DNP-Ficoll injections which cause virtually total blockade of 4th-day primary direct PFC responses to DNP-KLH have little or no effect on the development of DNP-reactive B-cell memory measured at either 8 or 30 days. These findings suggest very different blockade susceptibilities for B cells or their precursors at various stages of differentiative development. Our findings also lead to the formulation of testable hypotheses regarding the mechanism of this selective B-cell blockade phenomenon.
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D004136:Dinitrobenzenes / Q000276:immunology; D005260:Female; D008040:Genetic Linkage; D006241:Haptens / Q000276:immunology*; D007156:Immunologic Memory; D051379:Mice; D008808:Mice, Inbred CBA; D009154:Mutation; D011134:Polysaccharides / Q000276:immunology; D012730:Sex Chromosomes; D014960:X Chromosome
D004136:Dinitrobenzenes; D006241:Haptens; D011134:Polysaccharides