The architecture of the splenic white pulp is abnormal in ALPS patients. HES staining (A-D) and immunohistochemistry (IHC) (E-X) of paraffin sections of spleen specimens from control (A,E,I,J,Q,U) and from P-33 (B,F,K,L,R,V), P-46 (C,G,M,N,S,W), and Pm-1 (D,H,O,P,T,X). (A-D) HES staining revealed that patients had fewer follicles than controls (magnitude ×16). (E-H) IHC with an anti-CD3 antibody (magnitude ×25) showed normal PALSs in a control specimen (E) but revealed a striking expansion of the T-cell zone around the follicles (in place of MZ) in P-33 and P-46 (F-G). In Pm-1, nodules stained positive for CD3 (H). (K-P) As revealed by staining with specific antibodies, most of the T cells expressed neither CD4 (K,M,O) nor CD8 (L,N,P) (magnitude ×50) in ALPS patients. (Q-T) IHC with an anti-CD20 antibody (magnitude ×25) stained the follicles, mantle zone, and MZ in control spleen (Q). In P-33 and P-46, staining was positive in the follicles and the mantle zone but negative in the MZ. A ring of positive CD20⁺ cells (P-33) (R) or a few CD20(⁺) cells around the MZ were found in P-46 (S). In Pm-1, a few CD20⁺ cells were found in the follicle-free red pulp (T). (U-X,U’-X’) IHC with anti-CD1c antibody (U-X: magnitude ×100; U’-X’: amplification of framed area). Naïve B cells in the mantle zone are CD1c ^low, whereas MZ B cells are CD1c ^bright in control spleen (U,U’), P-33 (V,V’), P-46 (W,W’), and Pm-1 (X,X’).