Polyclonal activation of the murine immune system by an antibody to IgD. VIII. Stimulation of IgD secretion.
The low levels of serum IgD found in mice and the lack of a typical DNA switch sequence between C delta and C mu raise the possibility that the generation of murine IgD-secreting cells results from a chance "mistake" rather than a controlled process. The recent observation that injection of mice with purified IgD upregulates IgD receptor expression on helper T cells and enhances the ability of these T cells to induce B cells to differentiate into antibody secreting cells led us to look for evidence of controlled differentiation of B cells into IgD-secreting cells. To do this, we injected mice with a goat antibody to IgD (GaM delta), because this antibody stimulates large increases in IgM, IgG1, IgG2a, and IgE secretion. Mice injected with GaM delta demonstrated a large increase in splenic content of mRNA specific for the secreted form of delta-chain, as well as a greater than 100-fold increase in the percentage of splenic IgD-containing plasmablasts. The secretory IgD response was totally T-dependent. Production of the secretory form of IgD was not seen until 7 days after GaM delta injection, and peaked sharply on day 8, whereas by day 6 IgM secretion had already peaked and IgG1 and IgG2 secretion had attained substantial levels. This observation suggests that: 1) either cells that synthesize large quantities of the secretory form of delta-chain, unlike cells that synthesize large quantities of the secretory forms of gamma-, epsilon-, or alpha-chains, do this without deleting C mu, or, despite the absence of a typical DNA switch sequence between C mu and C delta, controls must exist to effect the C mu deletion and VDJ-C delta joining; and 2) if secreted IgD has a role in the regulation of a humoral immune response it most likely is involved in later processes, such as memory cell generation or response termination, rather than in relatively early processes, such as helper T cell activation.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D005260:Female; D005803:Genes, Immunoglobulin; D007127:Immunoglobulin Constant Regions / Q000235:genetics*; D007072:Immunoglobulin D / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000235:genetics; D007134:Immunoglobulin Switch Region / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology
D000888:Antibodies, Anti-Idiotypic; D007127:Immunoglobulin Constant Regions; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012333:RNA, Messenger; C039951:anti-IgD