Splenectomy Associated Changes in IgM Memory B Cells in an Adult Spleen Registry Cohort

Abstract

Asplenic patients have a lifelong risk of overwhelming post-splenectomy infection and have been reported to have low numbers of peripheral blood IgM memory B cells. The clinical value of quantitation of memory B cells as an indicator of splenic abnormality or risk of infection has been unclear. To assess changes in B cell sub-populations after splenectomy we studied patients recruited to a spleen registry (n = 591). A subset of 209 adult asplenic or hyposplenic subjects, and normal controls (n = 140) were tested for IgM memory B cells. We also determined a) changes in IgM memory B cells with time after splenectomy using the cross-sectional data from patients on the registry and b) the kinetics of changes in haematological markers associated with splenectomy(n = 45). Total B cells in splenectomy patients did not differ from controls, but memory B cells, IgM memory B cells and switched B cells were significantly (p<0.001) reduced. The reduction was similar for different indications for splenectomy. Changes of asplenia in routine blood films including presence of Howell-Jolly bodies (HJB), occurred early (median 25 days) and splenectomy associated thrombocytosis and lymphocytosis peaked by 50 days. There was a more gradual decrease in IgM memory B cells reaching a stable level within 6 months after splenectomy. IgM memory B cells as proportion of B cells was the best discriminator between splenectomized patients and normal controls and at the optimal cut-off of 4.53, showed a true positive rate of 95% and false positive rate of 20%. In a survey of 152 registry patients stratified by IgM memory B cells around this cut-off there was no association with minor infections and no registry patients experienced OPSI during the study. Despite significant changes after splenectomy, conventional measures of IgM memory cells have limited clinical utility in this population.

Proximal Versus Distal Splenic Artery Embolisation for Blunt Splenic Trauma: What is the Impact on Splenic Immune Function?

“…IgM memory B cell levels are reduced or absent in splenectomised and asplenic individuals [12,16,20,21]. A significant reduction or absence of IgM memory B cells is also found in patient groups with an intact spleen but known increased risk of invasive pneumococcal infection [18].…”

“…The methods used to assess IgM memory B cells have been described previously [12]. The levels of IgM memory B cells were then compared to the reference ranges previously established by the laboratory directed by one of the authors (PUC).…”

“…The levels of IgM memory B cells were then compared to the reference ranges previously established by the laboratory directed by one of the authors (PUC). The control group was selected from normal blood bank donors and represented a range of ages as previously described [12]. They were not age or sex matched to the donors.…”

Tissue Distribution and Dependence of Responsiveness of Human Antigen-Specific Memory B Cells

“…First, cluster of differentiation (CD) 27 + mBCs are present in the spleen (16), usually organized around B cell follicles (17)(18)(19). Splenectomy greatly diminishes peripheral mBC numbers of both CD27 + IgM + IgD + preswitch mBCs and CD27 + IgD 2 postswitch mBCs (20)(21)(22). Finally, mBCs generated during T cell-dependent (TD) responses persist in the spleen at increased numbers compared with peripheral blood (PB) even 30 y after the last Ag exposure (23).…”

Is the Spleen Really Important?

“…In some animal and clinical studies, there is clear evidence showing that the spleen absence increases host mortality [8,9].…”