MHC class II antigen presentation by B cells in health and disease

Abstract

MHC class II antigen presentation by B cells is important to activate CD4+ T cells that stimulate the B cell to produce antibodies. Besides this, disruption of MHC class II antigen presentation could play a role in immune escape by tumor cells. This thesis describes MHC class II antigen presentation by B cells during bacterial infections and leukemia. We show that, in contrast to the current dogma, human B cells are able to phagocytose whole, living Salmonella bacteria via their B cell receptor (BCR). Salmonella survives intracellular and is transported by the B cell to the spleen where Salmonella can infect other cells. Although Salmonella uses the B cell to disseminate and escape the immune system, uptake of Salmonella by B cells also results in a good immune response consisting of specific antibody production, antigen presentation and activation of both CD4+ T helper cells and cytotoxic CD8+ T cells that are able to eliminate infected cells. Many leukemic cells express MHC class II. For AML (acute myeloid leukemia) we show that expression of the self-peptide CLIP could be a measure for immune escape because a high percentage of HLA-DR+/CLIP- blasts correlates with a longer disease-free survival. In B-CLL (chronic lymphocytic leukemia), the percentage of activated CD4+ and CD8+ T cells is enhanced and inversely correlated to CLIP. In addition, transcription of all MHC class II genes is increased and B-CLL patients with high HLA-DOA mRNA levels have a less favorable prognosis.