Our results in humans have demonstrated that obesity-associated defects in class switch recombination (CSR) and somatic hypermutation (SHM), two processes necessary for the generation of class switched high affinity secondary antibodies (61), are due to reduced expression of activation-induced cytidine deaminase (AID), the enzyme of CSR and SHM, and E47, encoded by the E2A gene, a key transcription factor regulating AID (62). Here, TCF3 is linked to obesity due to melanocortin 4 receptor deficiency.