Aged B lymphocytes retain their ability to express surface markers but are dysfunctional in their proliferative capability during early activation events

摘要

Background Ageing is associated with dysfunction in the humoral response leading to decreased protection against infectious diseases. Defects in T cell function due to age have been well characterized but it is unclear if dysfunctions in antibody responses are due to deficiencies in a helper environment or intrinsic B cell defects. Previous studies from our laboratory have shown that aged B lymphocytes are able to differentiate into high affinity antibody-secreting cells at a frequency similar to their young counterparts. However, expansion of B cells in vivo was reduced in aged animals when compared to young. Methods To further investigate the cause of this reduced expansion, we have now examined early activation events of aged B cells in response to anti-CD40 monoclonal antibody (mAb) and lipopolysaccharide (LPS) stimulation in vitro. To do this spleen cells were harvested from young, middle-aged and aged quasi-monoclonal (QM) mice and cultured in complete RPMI for 24 and 48 hours. Cultures contained either LPS or anti-CD40 mAb and murine IL-4. Cells were collected and analyzed using flow cytometry. To examine the proliferative capacity of aged B cells spleen cells were collected as before and cultured in 96 well microtiter plates with either LPS or anti-CD40 mAb and murine IL-4 for 24 hours. Tritiated thymidine ([3H]-Tdr) was added to each well and incubated for another 24 hours after which cells were collected and analyzed using a scintillation counter. Results Resting aged B cells exhibited similar levels of CD40 expression when compared to young cells and efficiently up-regulated CD86 and CD69 and also down-regulated CD38 upon stimulation. However, aged B cells proliferated less than young B cells and showed a consistent, but not statistically significant, reduction in their ability to form blast cells. Conclusion Aged B cells exhibited a reduced response in some early activation events but produced at least a partial response in all cases. Thus, therapeutic intervention may be possible, despite intrinsically different responses in aged B cells.