Diagrammatic representation of the two subsets of chronic lymphocytic leukemia (CLL).

Conventionally, B cells meet antigen in the germinal center in the context of T cells and antigen presenting cells. This stimulates somatic mutation of the immunoglobulin V genes, and a memory B cell emerges from the germinal center. The unmutated subset might be explained by envisioning unconventional stimulation of the B cell receptor outside the germinal center, either by T-independent antigens or superantigen. This does not induce somatic mutation, but does stimulate an “experienced” immunophenotype.