B Cell Malignancies Frequently Target the Autoreactive B Cell Repertoire

Autoreactive B cells constitute a substantial part of B cell repertoire. They frequently secrete polyspecific natural autoantibodies, which are the expression of germinal genes. During recent years considerable evidence has accumulated indicating that this autoreactive B cell repertoire frequently undergoes malignant transformation. Studies on antibody activity of paraproteins and some B-cell malignancies have clearly demonstrated an impressive high frequency of autoantibody activity in these disorders. About 30% of IgM paraproteins and at least 10% of IgG and IgA monoclonal Ig display rheumatoid factor, cold agglutinin, anti-myelin associated glycoprotein or polyreactive activity. Similar high frequencies of autoantibody activity have been observed when CD5*** CLL B lymphocytes and CD5-follicular lymphoma B lymphocytes are induced to secrete Ig. The activation of this autoreactive B-cell repertoire through continuous challenge by self antigens could create suitable conditions for the occurrence of mutations and chromosomal translocations.