Abstracts (complete list) - Wissenschaft Online

Theresa Tretter, Ram Kumar Venigalla, Volker Eckstein, Hanns Martin Lorenz
Identification of human B cells with immunoregulatory
properties
Introduction: B cells are well known as mediators of humoral immunity and as antigen
presenting cells in generation of T cell mediated responses. However observations from
certain mouse models for autoimmunity point also to a role for B cells in maintaining
tolerance. So far little is known yet about their immunoregulatory properties,
specifically in humans and the mechanisms behind.
Methods: Highly purified CD19+B and CD4+T cells were separated from human PBMC
by MACS. B cells were prestimulated with SAC, aIgM/IgG or aCD40, and set up in
cocultures with autologous CD4+T cells under addition of aCD3 +IL-2 or aCD28. CD4+
T cell proliferation was determined after 3-6d by 3H Thymidine incorporation and PKH-
26; apoptosis by AnnexinV.
Results: under optimal stimulatory conditions T cell proliferation was inhibited by more
than 50% in presence of SAC-activated B cells and to a lesser extent by aIgM/IgG
stimulated B cells. There was a strong correlation with activation status of the B cell
since enrichment of the large SAC activated CD25+ B cell population by FACSsorting
further enhanced suppression to more than 70%, while the small SAC activated CD25-
B cell population had no significant effect. Separation of B and T cells by cell culture
inserts abolished inhibition, suggesting a requirement for direct cell-contact. In addition,
optimal stimulatory conditions were necessary for inhibitory effects since suppression
was not observed in absence of CD28 or exogenous IL-2. In addition to growth
inhibition, T cell specific cytokine production (IFN-gamma, IL-10) was downregulated,
and a significant proportion of T cells went into apoptosis.
Conclusions: B cells are able to inhibit T cell mediated responses depending on their
mode of activation. Further experiments are dealing with the mechanisms of B cell
mediated suppression and their pathophysiological impact also in autoimmune diseases.