Abstract: Human and animal serum contains naturally occurring autoantibodies that develop at birth in absence of deliberate immunization. These antibodies are predominantly of IgM isotype but can include all immunoglobulin isotypes such as IgD, IgA and IgG. Here we describe IgM anti-lymphocyte autoantibodies and show that these antibodies are heterogenous with some antibodies binding to chemokine receptors such as CCR5 and CXCR4 and others binding to other T cell receptors including CD3. IgM antibodies inhibit HIV-1 from infecting cells, inhibit chemokine from binding to receptors and inhibit activation and proliferation of T lymphocytes. IgM antibodies that bind to lymphocyte also bind to other leucocytes and other cells such as cancer cells and endothelial cells.