Nature 264, 780 - 782 (23 December 1976); doi:10.1038/264780a0

Evidence for the inactivation of precursor B cells in high dose unresponsiveness

CATHERINE DESAYMARD^*† & HERMAN WALDMANN^‡

^†Department of Experimental Immunobiology, Wellcome Research Laboratories, Beckenham, Kent BR3 3BS, UK
^‡Immunology Division, Department of Pathology, Tennis Court Road, Cambridge, UK
^*Present address. Centre Immunopathologie, Bâtiment INSERM, Hôpital Saint Antoine, F.75012 Paris, France.

THE mechanisms of tolerance induction, a state of specific antigen induced unresponsiveness in lymphocytes, are still ill understood. The impetus to generate information on these mechanisms derives from the practical importance of understanding "self-tolerance". Both T (thymus-derived) and B (bone marrow-derived) lymphocytes can be rendered specifically unresponsive to antigen. This paper examines the nature of the unresponsiveness induced in B cells by high doses of two types of antigen; firstly by a set of hapten conjugates known to be thymus-independent tntigens (DNP-SIII, DNP-Levan, DNP-Dextran)¹ and secondly by a known thymus-dependent conjugate (TNP-BSA). It is now well authenticated that for efficient antibody production B cells need to proliferate after which members of the proliferated clone may differentiate into antibody producers. It is therefore important to establish whether unresponsiveness induced in B cells occurs by inactivation of the precursor cell or by an effect on the derived clone. We here demonstrate that in vitro, B cell unresponsiveness induced by both kinds of antigens (thymus-dependent and independent) results solely from the inactivation of the precursor hapten specific B cells, so that these cells cannot expand into normal antibody producing clones, rather than by any mechanism which may have affected the clone size such precursor cells could yield.

References

1.	Desaymard, C., and Feldmann, M., Eur. J. Jmmun., 5, 537–541 (1975).
2.	Ly, I. A., and Mishell, R. I., J. Immun. Meth., 5, 239–247 (1974).
3.	Lefkovits, I., Eur. J. Immun., 2, 360–365 (1972).
4.	Quitans, J., and Lefkovits, I., Eur. J. Immun., 4, 617–220 (1974).
5.	Desaymard, C., and Howard, J. G., Eur. J. Immun., 5, 541–546 (1975).