Model for how defects in receptor editing can promote development of MBL and CLL. Non–self-reactive immature B cells arriving from the bone marrow progress normally through the immature/transitional stages of B-cell development where receptor editing normally occurs. An immature/T1 B-cell possessing an autoreactive specificity normally subjected to editing may acquire a spontaneous mutation that impairs receptor editing (RE), (modeled here by dnRAG1 expression), which enforces receptor specificity and leads the B cell to retain or adopt a CD5⁺ B1-like (and CLL-like) phenotype. The cell may persist or accumulate as an MBL, which may or may not require other mutations, such as those causing TCL1 overexpression. Additional genetic lesions may promote MBL evolution to CLL and perhaps subsequently to RS.³⁹  A similar series of events may also occur in post–germinal center B cells attempting to undergo receptor revision after having acquired autoreactivity during somatic hypermutation (not shown). T, transitional B cell; FM, follicular mature B cell; B1, B1 B cell; RS, Richter syndrome.