Mutated CLL B-cell development occurs initially in the bone marrow and subsequently in lymphoid
organs. In bone marrow, hematopoietic progenitor cells (HSC) differentiate into the pro-B cell that use
IGHV genes related with autoimmunity. The pro-B cell undergoes a rearrangement of its
immunoglobulin (Ig) heavy chain genes and is called a pre-B cell. Subsequent rearrangement of the
light chain enables the cell to express surface self reactive BCR that fail to be corrected by several
rounds of receptor edition. This self-reactive B cells enter in germinal centres and undergo somatic
hypermutation in order to negate their autoreactivity. This is the way in which this self-reactive CLL B
cells pass up tolerance mechanisms as germinal centre exclusion, however, fortunately they suffer some
mutations to reverse their self reactivity and avoid autoimmune diseases as SLE. These cells leave the
germinal center as mutated CLL B cells memory like cells.