Accumulation Of CD11c~+ B Cells Impair Antibody Affinity Selection

Antibody affinity maturation which takes place in germinal centers is the consequence of selection of high affinity antibodies.Antibody affinity maturation is very important for the immune response for they can protect us from invading of pathogens.For the complexity of the antibody affinity maturation,it can be affected by many factors.It is reported that there is aberrant antibody affinity maturation in the autoimmune mice model with Ship-deficient in B cells.And there are many reports about low response of vaccination in patients with autoimmune diseases or chronic inflammatory diseases.But the mechanism is not known.So,it is very important to make it clear how the impaired antibody affinity happens and it will be very useful for the treatment of immune-related disorders and high affinity antibodies development.We use the mice with Ship deficient in B cells as a model of impaired antibody affinity maturation.We find that the impaired antibody affinity maturation is not due to Ship defficiency in germinal center B cells as there is normal B cell germinal center selection when Ship deleted only in germinal center B cells.In fact,the inappropriate selection environment is responsible for the aberrant germinal center affinity maturation.There are more activated T cells in which many cells can secret IFN?and also accelerated accumulation of CD11c~+ABCs.We find that antibody germinal center selection can be impaired by T cell over activation.Once we delete IFN?,antibody germinal center selection can be back to normal.Antibody affinity maturation also can be reestablished by blocking Toll like receptor signaling which is important for CD11c~+ABCs'generation.We also find the same phenotype in pristane induced mice model.Our results suggest that over activation of T cells caused by accelerated ccumulation of CD11c~+ABCs in chronic inflammatory diseases and autoimmune diseases is the reason for impaired germinal center antibody affinity maturation.Our results will be very supportive in autoimmune diseases treanment and the development of antibodies with different affinity.