Genetic defect in human X-linked agammaglobulinemia impedes a maturational evolution of pro-B cells into a later stage of pre-B cells in the B-cell differentiation pathway.

摘要: Surrogate light chains (λ5/VpreB) are selectively expressed in early precursors of B cells. B-cell defects X-linked agammaglobulinemia (XLA) caused by mutations the gene for Bruton9s tyrosine kinase. To elucidate nature B-lineage cells bone marrow (BM), samples from 13 XLA patients and 24 healthy controls different ages were comparatively analyzed using an antihuman VpreB monoclonal antibody. Expression surrogate (SL) μ-heavy examined after cell membrane permeabilization because they mainly cytoplasm A flow cytometric analysis normal BM identified 5 discrete types cells: μ − SL ++ (pro-B [B-cell progenitor]), low (pre-B1a), + (pre-B1b), (pre-B2), high (B). The large cells, presumably cycling states, enriched pre-B1a frequencies higher young children, declined with advancing age. In contrast, showed a profound reduction BM, expansion pro-B some small was marked, but other negligible. These observations illustrate maturation defect as well human differentiation pathway. results suggest that genetic may impede evolution beyond earlier pre-B stage into later development.