Physiology of IgD. I. Compensatory phenomena in B lymphocyte activation in mice treated with anti-IgD antibodies.

Abstract

Classic studies by Rowe et al . (1) in the human and by Vitetta and coworkers (2) in the mouse have established that IgD is a major membrane immunoglobulin. This has led to a variety of studies and speculation regarding its biological function . Based upon the effect of anti-IgD on the in vitro primary response, Cambier et al. (3) suggested that the presence of IgD on the cell surface was critical for responses to thymus-dependent but not thymus-independent antigens . Prolonged in vivo treatment of mice with anti-IgD, starting at birth, was reported by Layton et al . (4) to result in a decrease in the incidence of IgD positive cells, accompanied by a depression in the secondary indirect plaque-forming cell, (PFC) i response . In contrast, Bazin et al . (5) found that treatment with antiserum to IgD from birth led to little or no decrease in any of the immunoglobulin classes except for IgE, which was markedly reduced . IgE antibody responses were also depressed .As in the case of the other immunoglobulin classes, allelic exclusion has been shown to exist for IgD (6, 7) . The availability of monoclonal allotype-specific antibody to IgD allows the investigation of the effects of anti-IgD in allotype heterozygous mice, with restriction of the effects limited to one halfof the B cell population . Comparison with the alternative allelic products permits a sensitive study of the role of IgD in immune responses with an ideal internal control . Furthermore, anti-IgD treatment of heterozygous or of homozygous mice might provide a clue to phenomena of internal balance and compensation (regulation) within an immune system . We therefore decided to re-investigate several aspects of the effects of anti-IgD on the immune system : (a) to compare the effect of anti-delta suppression in homozygous and heterozygous animals ; (b) to determine whether IgD suppression is linked to the suppression of the corresponding IgG allotypes ; and (c) to determine the effect of functional inactivation of all delta-positive cells on the development of germinal centers and on memory cell generation .

The origin of marginal zone B cells in the rat

“…The presence of memory(-like) cells (hapten-binding cells) in marginal zones after immunization has been established by MacLennan and co-workers [14,15,33]. Anti-IgD treatment does not seem to affect GC formation as was shown in mice [34,35]. These GC cells could contribute to marginal zone development in anti-IgD-treated animals.…”

Role of IgD and Tδ Cells in the Regulation of the Humoral Immune Response

“…The initial stimulus for germinal center production could involve such an interaction since, under normal conditions, IgD+ B cells (>90% of normal B cells) are the probable precursors of germinal centers (Seijen et al 1988). However, in mice treated from birth with anti-IgD, germinal center formation is not abolished (Jacobson et al 1981). In such mice, the remaining splenic B cells are all IgM"", IgD".…”

Functional anatomy of germinal centers

“…Furthermore, studies in rat and mouse indicate that GCPC originate from sp+6cells. Treatment of rats from birth with antip antibodies prevents the occurrence of all follicular lymphoid cells (Kumararatne et al, 19811, but treatment of mice from birth with anti4 antibodies allows the development of GC (while corona lymphocytes are absent) (Jacobson et al, 1981;Thorbecke et al, 1982;Finkelman et al, 1983). These data are compatible with GCC-B being s6-and corona lymphocytes being s6+.…”