IgM heavy chain complementarity-determining region 3 diversity is constrained by genetic and somatic mechanisms until two months after birth

Due to the greater range of lengths available to the third complementarity determining region of the heavy chain (HCDR3), the Ab repertoire of normal adults includes larger Ag binding site structures than those seen in first and second trimester fetal tissues. Transition to a steady state range of H CDR3 lengths is not complete until the infant reaches 2 mo of age, Fetal co nstraints on length begin with a genetic predilection for use of short D-H (D7-27 or DQ52) gene segments and against use of long D-H (e.g., D3 or DXP) and J(H) (J(H)(6)) gene segments in both fetal liver and fetal bone marrow , Further control of length is achieved through D-H-specific limitations in N addition, with D7-27 DJ joins including extensive N addition and D3-cont aining DJ joins showing a paucity of N addition, D-H-specific constraints o n N addition are no longer apparent in adult bone marrow. Superimposed upon these genetic mechanisms to control length is a process of somatic selecti on that appears to ensure expression of a restricted range of HCDR3 lengths in both fetus and adult, B cells that express Abs of an "inappropriate" le ngth appear to be eliminated when they first display IgM on their cell surf ace. Control of N addition appears aberrant in X-linked agammaglobulinemia, which may exacerbate the block in B cell development seen in this disease. Restriction of the fetal repertoire appears to be an active process, forci ng limits on the diversity, and hence range of Ab specificities, available to the young.