AIM, a murine apoptosis inhibitory factor, induces strong and sustained growth inhibition of B lymphocytes in combination with TGF-beta1.
Lymphocyte proliferation is stimulated by differential combinations of various cytokines, antigens and adhesion molecules. However, mechanisms of negative regulation in lymphocytes are poorly understood despite their potential importance in controlling the balance of lymphocyte proliferation, particularly at inflammatory sites. We recently reported a novel murine soluble protein, termed AIM, which inhibits apoptosis of a variety of cell types including CD4/CD8 double-positive thymocytes. AIM is secreted specifically by macrophages and belongs to the macrophage scavenger receptor cysteine-rich domain superfamily. Here we show that in addition to the apoptosis-inhibitory effect, AIM induces strong, long-term inhibition of B lymphocyte proliferation in combination with transforming growth factor-beta1 (TGF-beta1 in vitro), resulting in almost complete block of proliferation and immunoglobulin secretion. The function of AIM as a cell growth inhibitor requires pretreatment of B cells with TGF-beta1 which appears to increase expression of the AIM receptor on the B cell surface. Thus B lymphocyte proliferation is dramatically down-regulated by sequential exposition to TGF-beta1 followed by AIM. Like many cytokines, AIM has different functions depending on the types of target cells and the combination with other cytokines.
Yusa
S
S
Basel Institute for Immunology, Switzerland.
Ohnishi
S
S
Onodera
T
T
Miyazaki
T
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D001402:B-Lymphocytes / Q000187:drug effects*; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D011971:Receptors, Immunologic / Q000502:physiology*; D051116:Receptors, Scavenger; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D051017:Apoptosis Regulatory Proteins; C117272:Cd5l protein, mouse; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D016212:Transforming Growth Factor beta