How would the transition from normal B cells to leukemic cells via antigen stimulation occur? Normal B lymphocytes using unmutated IgV genes produce antibodies that are frequently polyreactive, binding carbohydrates, nucleic acids and phospholipids. Such antibodies provide the first line of defense against microorganisms and promote the clearance of autoantigens and their fragments. B-CLL cells frequently display polyreactive BCRs, thereby making it possible that they derive from normal polyreactive B lymphocytes that have been repeatedly stimulated in vivo by a combination of nonprotein self and microbial antigens.
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