Under normal conditions, the colorectal mucosa exhibits small numbers of scattered lymphocytes and plasma cells in the lamina propria and only few mucosal lymphoid aggregates (MLAs). In Crohn's colitis, the number of lymphocytes and plasma cells in the lamina propria and of MLA is substantially increased. In addition, multiple lymphoid aggregates are newly formed in the submucosa (submucosal lymphoid aggregate (SLA)) and deeper. The aim of the present study was to investigate the cellular immune response in MLA, in SLA, and in the lamina propria in Crohn's colitis. Fifty-nine colorectal biopsies/surgical specimens with or without inflammatory diseases were challenged with multiple myeloma 1 (MUM1) that highlights activated T cells, committed B cells, and plasma cells (aT/cB/PC). The number of MUM1-positive aT/cB/PC per high-power field (HPF) in MLA and in SLA was significantly lower in Crohn's colitis than in controls (p < 0.05). In contrast, the number of MUM1-positive aT/cB/PC per HPF in the lamina propria was significantly higher in Crohn's colitis and in other forms of chronic colitis than in controls (p < 0.05). The paucity of MUM1-positive cells in MLA and in SLA in Crohn's colitis might be caused by an increased number of MUM1-negative precursors. These precursors would eventually migrate into the lamina propria to differentiate into aT/cB/PC, complying thereby with the immunological mucosal demands generated by the on-going chronic inflammation.