CD45RA and RO isoforms have distinct effects on cytokine- and B-cell-receptor-mediated signalling in human B cells.
The common leucocyte antigen, CD45, is widely expressed on the surface of lymphocytes. In T and B cells, CD45 has an important role in the early events of receptor signalling. However, the role of various CD45 isoforms in B-cell receptor (BCR)- and cytokine-induced signalling and proliferation is still unclear. In the present study, we establish two follicular lymphoma cell lines expressing either CD45RA (HF28RA) or CD45R0 (HF28R0) isoforms. It was observed that the two isoforms had distinct effects on BCR- or cytokine-induced cellular proliferation. BCR stimulation significantly increased the proliferation of HF28R0 cells, in contrast to a decreased proliferation of HF28RA cells. Moreover, proliferation of HF28R0 cells significantly increased after the addition of interleukin-2 (IL-2), IL-4, IL-6, IL-10, IL-12, IL-13, IL-15, interferon-gamma and tumour necrosis factor-alpha cytokines, whereas most of these cytokines significantly inhibited the proliferation of HF28RA cells. In addition, the cell lines had their individual cytokine mRNA expression profiles after BCR stimulation. We also analysed the effect of CD45 isoforms on intracellular signalling after BCR stimulation. It was found out that the kinetics of ERK1/2 MAP kinase phosphorylation was clearly faster in HF28R0 than in HF28RA cells. The phosphorylation of other analysed MAP kinases or PTKs was very similar in the cell lines.
Mättö
M
M
Department of Clinical Microbiology, University of Kuopio, Kuopio, Finland. mikko.matto@uku.fi
Nuutinen
U-M
UM
Ropponen
A
A
Myllykangas
K
K
Pelkonen
J
J
D001402:B-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D045744:Cell Line, Tumor; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction
D016207:Cytokines; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D048052:Mitogen-Activated Protein Kinase 3; D017493:Leukocyte Common Antigens