The murine humoral immune response to HBs antigen(Ag) has previously been demonstrated to be rcgulated by H-2-linked Ir genes. For example, SJL/J mouse(H-2Es) does not produce anti-HBs antibody(Ab) after the immunization with HBeAg/P25, where as
BALB/C(H-2Ed) and F((SJL/J(BALB/C) mice make high titers of anti-HBsAb In vitro experimental data have een accumulated to indicate the strong possibility that the antigen presenting calls(APC) of SJL/J mice have HBsAg specific defect(s).
SJL/J and F( mice are genetically haploidentical so that the APC of the either can present antigens to the T cells of the other. In addition to this, the APC of F( mouse are reported to be able to present HBsAg to T cells.
In this communication, we tried to circumvent the HBsAg specific defect in the APC of SJL/J mouse by immunizing the SJL/J mouse with F( APC pulsed with HBsAg in vitro, and following results were obtained.
1. No anti-HBsAb production, HBsAg specific T cell proliferative response, or the IL-2 production of HBsAg specific T cells was noted after inoculating SJL/J mice with HBsAg/P25. On the contrary, in case of BALB/C and F( mice, high titers of
anti-HBsAb
production, high HBsAg specific T cell proliferative responses, and IL-2 production were observed.
2. When the APC of F( mouse after the in vitro HBsAg pulse were injected into SJL/J mice iv, SJL/J mice produced as much anti-HBsAb as BALB/C or F( mice did after the HBsAg injection. But the trials with the BALB/C APC via iv or ip route, the F(
APC via
ip route, and the simple mixture of the BALB/C(of F() APC and HBsAg failed to induce anti-HBsAb in SJL/J mice. And, after the secondary immunization with HBsAg following the primary one with the HBsAg pulsed F( APC to SJL/J mice, the same levels
of
antibodies were produced in SJL/J mice as after the primary and secondary immunization with the HBsAg pulsed F( APC. Without any secondary immunization, no antibodies were detected thereafter.
3. The IL-2 production of HBsAg specific T cells was measured after injecting the HBsAg pulsed APC into footpads of SJL/J mice. The APC were heat treated (45℃ for 1 hour) to reduce the allostimulation, if they were from BALB/C or F( mice. Or,
they
were
treated with mitomycin C, when they were from SJL/J mice. T cells from SJL/J mice(injected with the HBsAg puilsed & heat treated F( APC) produced IL-2. But, T cells from all the other SJL/J mice(injected with the HBsAg pulsed & mitomycin Cheat>
treated SJL/JAPC) failed to produce IL-2.
These results indicate that the HBsAg specific immunological defect in the APC of SJL/J mice can be circumvented by immunizing the SJL/J mouse with the F( APC pulsed with HBsAg in vitro, which are functionally competent and can present HBsAg to
the
T
clarify the because these two cells share one H-2 haplotype. Further studies are required to clarify the immunological defects in the hepatitis B vaccine nonresponders and to apply these techniques to human.
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