In vitro studies on human IgD II. IgD-secreting cells preferentially elaborate IgD, λ molecules
✍ Scribed by Stephen D. Litwin; Bradley D. Zehr
- Book ID
- 102161550
- Publisher
- John Wiley and Sons
- Year
- 1987
- Tongue
- English
- Weight
- 475 KB
- Volume
- 17
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
In vitro studies on human IgD 11. IgD-secreting cells preferentially elaborate IgD,h molecules
The "IgD paradox" describes the unexpected finding that, despite a predominance of kappa ( x ) light (L) chains on the surface of IgD' human B cells, the majority of monoclonal IgD proteins are of lambda (A) type. This potentially informative phenomenon appears to be based on a preferential association between delta (6) heavy (H) and h L chains of IgD-secreting cells. The current studies analyze the phenomenon in vitro. Initial assays on tonsil "spent" supernatants showed that the higher IgD-"externalizing" cultures displayed progressively elevated IgD,hlx ratios due to parallel shifts in total IgD and IgD,h while IgD,n remained stable. The cells of the same higher-IgD cultures demonstrated that individual IgD-containing cells had a predominance of h chains in contrast to IgM-containing cells of the same cultures using fluorochrome-antibody double staining. Certain tonsil culture IgD-containing cells remarkably appeared to have exclusively h chain. These same tonsils show evidence of IgD secretion (Litwin, S. D. and Zehr, B. D., Eur. . I .
Immunoi. 1987.17: 483); thus, these data align preferential 6-h chain association with IgD-secreting normal tonsil B cells in vitro and emphasize the usefulness of IgD ,h/n ratio in monitoring IgD secretion. In another approach the relationship between the cellular location of IgD and the preferential 6-h chain association was studied using Triton X-114partitioned cell lysates. IgD,h/x ratios were one or less in the detergent phase (membrane-enriched fraction) consistent with expected IgD ,n predominance in membrane IgD. In contrast, the aqueous phase (intracellular-enriched fraction) of IgD-secreting cultures had 2-4 times higher supernatant IgD ,hlx ratios. The restriction of high IgD,hlx ratios to intracellular fractions and supernatants of IgD-secreting cultured cells parallels the predicted distribution of secretory IgD. In sera studies, the correlation between total IgD and IgD,h/x ratio values was consistent with secreted sera IgD showing preferential k chain expression. It was concluded that the phenomenon of 6-1 chain preferential association is (a) expressed in vitro as well as in vivo; (b) a property of normal, nonmalignant human IgD-secreting B cells; and (c) closely related to the secretory form of IgD. In certain cultures, the 6-1 chain preference was so striking as to imply limited heterogeneity of the IgD immune response.