Antigen-specific Antibody Secreting Research Articles

Age-related changes of the antigen-specific antibody formation in vitro and PHA-induced T-cell proliferation in individuals who met the health criteria of the senieur protocol

The antigen-specific antibody secretion in vitro after immunisation with the primary T-cell dependent antigen Helix pomatia Haemocyanin (HPH) was investigated in both young and elderly individuals, who all met the health admission criteria for immunogerontological studies as detailed in the SENIEUR protocol. In addition, elderly non-Senieur persons were incorporated in this study. Young and elderly Senieur volunteers were fully comparable in terms of the occurrence of anti-HPH antibody secreting cells after in vitro simulation of peripheral blood mono-nuclear cells with variable doses of the antigen. In contrast, the non-Senieur elderly showed a lower number of anti-HPH antibody secreting cells in vitro. PHA-conditioned medium did enhance this in vitro response, whereas the addition of IL-2 remained ineffective. The PHA-induced T-cell proliferation was found to be somewhat impaired in elderly Senieur individuals and significantly lower in elderly non-Senieur individuals compared to young healthy persons. Using an immunofluorescence double staining technique after BrdU incorporation, the phenotype of the proliferating cells was determinated. Again the total number of proliferating cells was impared in the non-Senieur elderly. No changes in the relative contribution of CD4 + or CD8 + cells to the number of proliferating cells were found in the different age groups. On the other hand, a significantly lower number of proliferating cells with IL-2 receptor expression were detected in the non-Senieur individuals, which could account for the lack of response to IL-2 in this group. Our study clearly shows vitro in a manner which is almost comparable to young healthy individuals although the variability of the response is increased. The impaired immune responsiveness, as seen in the non-Senieur elderly, may well have been caused by the influence of disease or medication and not solely by the process of ageing. This may result in a lack of, or unresponsiveness to, regulatory factors which need not necessarily be IL-2 alone. In this respect, further studies are essential, in which currently available recombinant factors, such as IL-4, IL-5 or IL-6 are added to the cultures for the induction of anti-HPH SFC. Furthermore, it will be interesting to analyze (HPH-specific) T-cell clones, obtained from young and old Senieur persons and non-Senieur individuals, for their profile of lymphokine secretion. In any case, it is essential to minimalize influences of disease or medication when carrying out such investigations and to select old and young donors according to the Senieur criteria.

T cell derived IL-6 is differentially required for antigen-specific antibody secretion by primary and secondary B cells.

IL-6 (formerly PCTGF, HP-1, BSF-2, HGF, IFN-beta 2, 26 kDa) is a recently defined lymphokine demonstrating activity on multiple cell types, including hepatocytes, thymocytes, T cells, plasmacytomas, and B cells. The biologic effects of IL-6 on lymphocytes, particularly B cells, suggest this factor may be involved in the regulation of normal immune responses. Accordingly, we have investigated the role of IL-6 in Ag-specific responses of B cells from both naive and Ag-primed mice. When Ag-primed splenic T cells were used as a source of help, naive (primary) B cell responses specific for the hemagglutinin molecule of the influenza A virus (PR8) were fully inhibited by the addition of an anti-IL-6 antiserum, and are thus IL-6 dependent. In contrast, secondary B cell responses were essentially IL-6 independent, being unaffected by this antiserum even at concentrations 10-fold higher than required to completely inhibit primary responses. This differential IL-6 requirement was further investigated by using a panel of hemagglutinin molecule-specific Th clones. Consistent with the above findings, a Th1 clone secreting biologically active IL-6 enables antibody secretion by both primary and secondary B cells, whereas Th1 clones that do not produce IL-6 support secondary responses, but fail to help primary B cell responses unless exogenous IL-6 is added. These results provide the first instance of differential lymphokine requirements among primary vs secondary B cell responses, and suggest T cell-derived IL-6 plays a critical role during the regulation of humoral immune responses. Moreover, functionally distinct Th1 clones were identified that differed in IL-6 secretion and their corresponding ability to induce Ig secretion by primary and secondary B cells.