Alley C D, Kiyono H, McGhee J R
J Immunol. 1986 Jun 15;136(12):4414-9.
Specific immunization protocols have been established for the induction of murine bone marrow IgA responses to the T cell-dependent (TD) antigen sheep red blood cells (SRBC). Systemic immunization, either i.p. or i.v., followed by a second injection, induced splenic IgM and IgG responses and a bone marrow IgM response. No significant IgA responses were observed in either lymphoid tissue compartment. Oral immunization with SRBC by gastric intubation for 2 days, followed 1 wk later by an i.p. injection of SRBC resulted in a splenic IgA plaque-forming cell (PFC) response, but did not elicit a bone marrow IgA response. Repeated daily gastric intubation of SRBC to C3H/HeN and C3H/HeJ mice led to the previously reported pattern of systemic unresponsiveness in C3H/HeN mice and good anamnestic type IgM, IgG, and IgA splenic anti-SRBC PFC responses in the C3H/HeJ strain upon parenteral challenge. Oral administration of SRBC for 14 days to C3H/HeN mice, followed by systemic SRBC challenge, resulted in diminished splenic PFC responses of all isotypes, whereas gastric intubation of SRBC for 28 days led to complete systemic unresponsiveness to antigen in C3H/HeN mice. Interestingly, the repeated oral administration of SRBC resulted in significant bone marrow IgA PFC responses upon i.p. challenge in both C3H/HeN and C3H/HeJ mouse strains. The bone marrow IgA responses were clearly dependent upon chronic oral exposure to SRBC, because gastric intubation with SRBC for 2 consecutive days/wk for 10 wk also induced bone marrow and splenic IgA anti-SRBC PFC responses in C3H/HeN mice. These results suggest that memory B cells reside in the bone marrow of orally immunized mice and can yield anamnestic-type responses to challenge with the inducing antigen. The memory cells may arise in the Peyer's patches of the gut and migrate to the bone marrow. The possibility that the bone marrow is a component of the common mucosal immune system in mammals is suggested by this study.
已建立特定的免疫方案，用于诱导小鼠骨髓对T细胞依赖性（TD）抗原绵羊红细胞（SRBC）产生IgA应答。腹腔内或静脉内进行全身免疫，随后进行第二次注射，可诱导脾脏产生IgM和IgG应答以及骨髓产生IgM应答。在两个淋巴组织区室中均未观察到明显的IgA应答。通过胃插管对SRBC进行2天的口服免疫，1周后腹腔内注射SRBC，可导致脾脏IgA斑块形成细胞（PFC）应答，但未引发骨髓IgA应答。对C3H/HeN和C3H/HeJ小鼠每日重复进行SRBC胃插管，导致C3H/HeN小鼠出现先前报道的全身无反应模式，而C3H/HeJ品系在经肠胃外攻击后产生良好的记忆型IgM、IgG和IgA脾脏抗SRBC PFC应答。对C3H/HeN小鼠口服SRBC 14天，随后进行全身SRBC攻击，导致所有同种型的脾脏PFC应答减弱，而对SRBC进行28天的胃插管导致C3H/HeN小鼠对抗原完全产生全身无反应。有趣的是，重复口服SRBC在C3H/HeN和C3H/HeJ小鼠品系腹腔内攻击后均导致显著的骨髓IgA PFC应答。骨髓IgA应答显然依赖于长期口服接触SRBC，因为每周连续2天对C3H/HeN小鼠进行SRBC胃插管，持续10周，也可诱导骨髓和脾脏产生IgA抗SRBC PFC应答。这些结果表明，记忆B细胞存在于口服免疫小鼠的骨髓中，并且可以对诱导抗原的攻击产生记忆型应答。记忆细胞可能在肠道的派尔集合淋巴结中产生并迁移至骨髓。这项研究表明，骨髓可能是哺乳动物共同黏膜免疫系统的一个组成部分。
