Journal of Experimental Medicine, Vol 154, 921-934, Copyright © 1981 by Rockefeller University Press

ARTICLES

Monoclonal antibody to an IgD allotype induces a new type of allotype suppression in the mouse

T Tokuhisa, FT Gadus, LA Herzenberg and LA Herzenberg

Studies presented here show that perinatal exposure to anti-IgD allotype antibodies induces a persistant IgG-allotype suppression in the mouse that differs markedly from either the short-term or chronic allotype suppressions induced by antibodies to IgG or IgM allotypes. This novel form of allotype suppression induced by injecting neonatal BALB/c x SJL mice with monoclonal antibody to the paternal Igh-5b (IgD) allotype drastically reduces paternal allotype production during the first 6 mo of the affected animal's life and simultaneously stimulates compensatory production of maternal allotype IgG. In addition, it interferes with the development of B cells carrying the paternal IgD allotype and impairs the development of memory B cells destined to give rise to paternal allotype IgG-producing cells. Thus, its properties make it more like allotype suppression as described in the rabbit than like the known forms of allotype suppression in the mouse. As shown here, Igh-5b-bearing (5b+) B cells are completely depleted from the neonate after anti-5b exposure and only gradually appear as the animal ages. The recovery of the 5b+ population to near normal size (by approximately 14 wk of age) substantially preceeds recovery of the ability to generate normal-size memory B cell populations. Paternal allotype levels in serum remain well below normal until the anti-5b- exposed animals reach approximately 6 mo of age and then climb rapidly, finally stabilizing at levels comparable to levels in controls of the same age. The elevated maternal allotype levels characteristic of the suppression period began falling somewhat earlier and are clearly stabilized within the normal range in 6-mo-old animals. Thus, perinatal exposure to anti-5b compromises B cell development and IgG production throughout early adulthood but has little apparent effect in older animals. Perinatal exposure to antibody to the paternal IgG2a allotype (Igh-1b) or IgM allotype (Igh-6b), in contrast, induces a chronic allotype suppression that has relatively little affect on IgG production in young adults but severely suppresses allotype production in older animals. Furthermore, this type of (chronic) suppression does not influence maternal allotype production and does not interfere with memory B cell development. These differences, illustrated here by data from parallel sets of animals exposed either toi anti-5b or anti-1b, raise a series of intriguing questions concerning the mechanisms regulating B cell development and expression and the nature of the neonatal (B) cell populations with which the suppression-inducing antibodies react.
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