TBL1XR1 mutation promotes a memory B-cell fate and germinal center reentry. (A) In TBL1XR1 wild-type GCB cells, the SMRT–HDAC3 complex preferentially associates with BCL6 and facilitates expansion of GCB cells in the DZ of the germinal center. These can terminally differentiate via the LZ into either plasma cells or memory B cells. Upon antigen rechallenge (blue arrows), memory B cells become antibody-secreting plasma cells, and a small subset reenters germinal centers. (B) Mutant TBL1XR1 (red) acts as a dominant negative to increase association between the SMRT–HDAC3 complex and the BACH2 transcription factor and to decrease association with BCL6. This leads to reduced frequencies of GCB cells and promotes a memory B-cell fate. Upon antigen rechallenge (blue arrows), a reduced frequency of TBL1XR1 mutant memory B cells become plasma cells, and an increased frequency reenter germinal center reactions and undergo additional somatic hypermutation.