Comparison of lgD+ and lgD− thoracic duct B lymphocytes as germinal center precursor cells in the rat

• Published in: International immunology 1991-12, Vol.3 (12), p.1273-1281
• Main Authors: Vonderheide, Robert H., Hunt, Simon V.
• Format: Article
• Language: English
• Subjects: germinal center; lgD; memory B cell
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/3.12.1273

Genetically marked thoracic duct B cell subpopulations rich in either lgD+ or lgD−B cells were transferred to non-irradiated, congenic rats in order to compare the capacities of lgD+ versus lgD− B cells to form germinal centers (GCs). This comparison was made quantitatively based on flow cytometric analyses of lymph node cells prepared from chimeric rats 7 days after s.c. immunization. Donor-origin and host-origin B cells were distinguished using anti-lgk antibodies, and GC B cells were distinguished from other B cells in suspension by their lack of labeling with the mAb HIS22. lgk+HIS22− lymph node cells corresponded well to GC B cells: they contained many large cells, were lgM+ but mostly lgD−, expressed relatively lower levels of IgM than HIS22+ B cells, and increased in number and frequency in response to antigen. Results from flow cytometric analyses, corroborated by immunofluorescence histochemical studies, showed that cell-for-cell, IgD− B cells form GCs much more efficiently than lgD+ cells. B cell populations enriched for lgD− cells became relatively more distributed to GCs than to other lymph node B cell areas and gave rise to many more GC B cells of donor origin per transferred B cell than whole, unseparated thoracic duct B cells (for which >97% were lgD+). lgD− B cells from rats primed deliberately with antigen also became relatively more distributed to GCs and gave rise to more GC B cells of donor origin than either lgD+ B cells from primed donors or lgD− B cells from unprimed donors. However, B cells from primed rats failed to participate actively in GC formation when transferred either to host rats which had been primed 2 months previously with the homologous antigen or to unprimed hosts subsequently challenged with a heterologous, non-cross-reacting antigen. To the extent that IgD+ thoracic duct B cells represent a long-persisting population of memory B cells, findings here suggest that upon secondary challenge, memory B cell populations actively help form new GCs contributing to the expansion and maintenance of the memory B cell pool.