Extrafollicular proliferation of B cells in the absence of follicular hyperplasia:: a distinct reaction pattern in lymph nodes correlated with primary or recall type responses

Aims: Extrafollicular activation of B cells is rarely observed in human lymph nodes. The aim of this study was to extensively analyse the expression of surface molecules and transcription factors in four such cases, comparing them with follicular B cells and medullary cord plasma cells. Methods and results: Various combinations of B-cell-related surface markers and transcription factors were studied by triple immunofluorescence. While in the germinal centre, reactive immunoglobulin production occurred exclusively in non-proliferating cells, in extrafollicular activation proliferation of B cells and immunoglobulin production coexisted. In two of these cases proliferating cells were mainly IgG+CD27+, i.e. derived from class-switched postgerminal centre memory B cells. Some of these cells expressed CD30. In the other two cases, immunoglobulin-forming cells were non-class-switched IgM+CD27- B cells, representing a primary expansion of naive B cells. Conclusions: Extrafollicular B-cell activation is the morphological correlate of rapid B-cell responses that do not involve the germinal centres. It is pathogenetically heterogeneous, comprising primary responses that occur prior to, or independent of, germinal centre reaction or memory cell activation in recall responses.